trying...<BR><?xml version="1.0" encoding="UTF-8" ?>
<!DOCTYPE eSearchResult PUBLIC "-//NLM//DTD esearch 20060628//EN" "https://eutils.ncbi.nlm.nih.gov/eutils/dtd/20060628/esearch.dtd">
<eSearchResult><Count>14</Count><RetMax>1</RetMax><RetStart>0</RetStart><QueryKey>1</QueryKey><WebEnv>MCID_676f08701613efaaf007d82d</WebEnv><IdList>
<Id>30987671</Id>
</IdList><TranslationSet><Translation>     <From>Timea Besenyei[author]</From>     <To>Besenyei, Timea[Full Author Name]</To>    </Translation></TranslationSet><QueryTranslation>besenyei, timea[Author]</QueryTranslation></eSearchResult>
trying2...<BR>trying...<BR><?xml version="1.0" ?>
<!DOCTYPE PubmedArticleSet PUBLIC "-//NLM//DTD PubMedArticle, 1st January 2024//EN" "https://dtd.nlm.nih.gov/ncbi/pubmed/out/pubmed_240101.dtd">
<PubmedArticleSet>
<PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30987671</PMID><DateCompleted><Year>2020</Year><Month>05</Month><Day>13</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>13</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1478-6362</ISSN><JournalIssue CitedMedium="Internet"><Volume>21</Volume><Issue>1</Issue><PubDate><Year>2019</Year><Month>Apr</Month><Day>15</Day></PubDate></JournalIssue><Title>Arthritis research &amp; therapy</Title><ISOAbbreviation>Arthritis Res Ther</ISOAbbreviation></Journal><ArticleTitle>Gene expression analysis of vascular pathophysiology related to anti-TNF treatment in rheumatoid arthritis.</ArticleTitle><Pagination><StartPage>94</StartPage><MedlinePgn>94</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">94</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1186/s13075-019-1862-6</ELocationID><Abstract><AbstractText Label="OBJECTIVES">Impaired vascular pathophysiology and increased cardiovascular (CV) mortality are associated with rheumatoid arthritis (RA). To date, no genomic analysis of RA- and RA treatment-related vascular pathophysiology has been published. In this pilot study, we performed gene expression profiling in association with vascular pathophysiology in RA patients.</AbstractText><AbstractText Label="METHODS">Sixteen and 19 biologic-na&#xef;ve RA patients were included in study 1 and study 2, respectively. In study 1, genetic signatures determined by microarray were related to flow-mediated vasodilation (FMD), pulse-wave velocity (PWV), and common carotid intima-media thickness (IMT) of patients. In study 2, clinical response (cR) vs non-response (cNR) to 1-year etanercept (ETN) or certolizumab pegol (CZP) treatment, as well as "vascular" response (vR) vs non-response (vNR) to biologics, were also associated with genomic profiles. Multiple testing could not be performed due to the relatively small number of patients; therefore, our pilot study may lack power.</AbstractText><AbstractText Label="RESULTS">In study 1, multiple genes were up- or downregulated in patients with abnormal vs normal FMD, IMT, and PWV. In study 2, there were 13 cR and 6 cNR anti-tumor necrosis factor (TNF)-treated patients. In addition, 10, 9, and 8 patients were FMD-20%, IMT-20%, and PWV-20% responders. Again, vascular responder status was associated with changes of the expression of various genes. The highest number of genes showing significant enrichment were involved in positive regulation of immune effector process, regulation of glucose transport, and Golgi vesicle budding.</AbstractText><AbstractText Label="CONCLUSION">Differential expression of multiple genetic profiles may be associated with vascular pathophysiology associated with RA. Moreover, distinct genetic signatures may also be associated with clinical and vascular responses to 1-year anti-TNF treatment.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>P&#xf3;liska</LastName><ForeName>Szil&#xe1;rd</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, University of Debrecen Faculty of Medicine, Debrecen, Hungary.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Sports Medicine, University of Debrecen Faculty of Medicine, Debrecen, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Internal Medicine, University of Debrecen Faculty of Medicine, Debrecen, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>V&#xe9;gh</LastName><ForeName>Edit</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hamar</LastName><ForeName>Attila</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pusztai</LastName><ForeName>Anita</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>V&#xe1;ncsa</LastName><ForeName>Andrea</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bodn&#xe1;r</LastName><ForeName>N&#xf3;ra</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Szamosi</LastName><ForeName>Szilvia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Csumita</LastName><ForeName>M&#xe1;ria</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, University of Debrecen Faculty of Medicine, Debrecen, Hungary.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Sports Medicine, University of Debrecen Faculty of Medicine, Debrecen, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kerekes</LastName><ForeName>Gy&#xf6;rgy</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Angiology, University of Debrecen Faculty of Medicine, Debrecen, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Szab&#xf3;</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nagy</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sz&#x171;cs</LastName><ForeName>Gabriella</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sz&#xe1;nt&#xf3;</LastName><ForeName>S&#xe1;ndor</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Sports Medicine, University of Debrecen Faculty of Medicine, Debrecen, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zahuczky</LastName><ForeName>G&#xe1;bor</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>UD Genomed Ltd., Debrecen, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nagy</LastName><ForeName>L&#xe1;szl&#xf3;</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology, University of Debrecen Faculty of Medicine, Debrecen, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, University of Debrecen Faculty of Medicine, Nagyerdei str 98, Debrecen, 4032, Hungary. szekanecz.zoltan@med.unideb.hu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>GINOP-2.3.2-15-2016-00050</GrantID><Agency>European Union</Agency><Country>International</Country></Grant><Grant><GrantID>TAMOP-4.2.4.A/2-11/1-2012-0001</GrantID><Agency>European Union</Agency><Country>International</Country></Grant><Grant><GrantID>GINOP-2.3.2-15-2016-00015</GrantID><Agency>European Union</Agency><Country>International</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>04</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Arthritis Res Ther</MedlineTA><NlmUniqueID>101154438</NlmUniqueID><ISSNLinking>1478-6354</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014409">Tumor Necrosis Factor-alpha</NameOfSubstance></Chemical><Chemical><RegistryNumber>OP401G7OJC</RegistryNumber><NameOfSubstance UI="D000068800">Etanercept</NameOfSubstance></Chemical><Chemical><RegistryNumber>UMD07X179E</RegistryNumber><NameOfSubstance UI="D000068582">Certolizumab Pegol</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059168" MajorTopicYN="N">Carotid Intima-Media Thickness</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000068582" MajorTopicYN="N">Certolizumab Pegol</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000068800" MajorTopicYN="N">Etanercept</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020869" MajorTopicYN="N">Gene Expression Profiling</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010865" MajorTopicYN="N">Pilot Projects</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D063177" MajorTopicYN="N">Pulse Wave Analysis</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014409" MajorTopicYN="N">Tumor Necrosis Factor-alpha</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists &amp; inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014664" MajorTopicYN="N">Vasodilation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Atherosclerosis</Keyword><Keyword MajorTopicYN="N">Certolizumab pegol</Keyword><Keyword MajorTopicYN="N">Etanercept</Keyword><Keyword MajorTopicYN="N">Gene expression</Keyword><Keyword MajorTopicYN="N">Genetic signature</Keyword><Keyword MajorTopicYN="N">Prediction</Keyword><Keyword MajorTopicYN="N">Response</Keyword><Keyword MajorTopicYN="N">Rheumatoid arthritis</Keyword><Keyword MajorTopicYN="N">Vascular pathology</Keyword></KeywordList><CoiStatement>AUTHORS&#x2019; INFORMATION: See above, cover page. ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The Medical Research Council of Hungary gave ethical approval for this study (No. 9732-2/2012/EHR). In addition, the Institutional Review Board of the University of Debrecen Faculty of Medicine also approved the protocol. The study that was in compliance with the Helsinki Declaration. Ethical approval (No. 1046-63/2015) was obtained from the Regional/Institutional Review Board of Miskolc University. All patients signed informed consent. The study was performed according to the Declaration of Helsinki. CONSENT FOR PUBLICATION: No data that could identify single patients are presented therefore this consent is not needed. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER&#x2019;S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>10</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>3</Month><Day>8</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>4</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>4</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>5</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2019</Year><Month>4</Month><Day>15</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30987671</ArticleId><ArticleId IdType="pmc">PMC6466794</ArticleId><ArticleId IdType="doi">10.1186/s13075-019-1862-6</ArticleId><ArticleId IdType="pii">10.1186/s13075-019-1862-6</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Kerekes G, Soltesz P, Nurmohamed MT, Gonzalez-Gay MA, Turiel M, Vegh E, Shoenfeld Y, McInnes I, Szekanecz Z. Validated methods for assessment of subclinical atherosclerosis in rheumatology. Nat Rev Rheumatol. 2012;8(4):224&#x2013;234. doi: 10.1038/nrrheum.2012.16.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrrheum.2012.16</ArticleId><ArticleId IdType="pubmed">22349611</ArticleId></ArticleIdList></Reference><Reference><Citation>Kerekes G, Szekanecz Z, Der H, Sandor Z, Lakos G, Muszbek L, Csipo I, Sipka S, Seres I, Paragh G, et al. Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity. J Rheumatol. 2008;35(3):398&#x2013;406.</Citation><ArticleIdList><ArticleId IdType="pubmed">18203326</ArticleId></ArticleIdList></Reference><Reference><Citation>PETERS MIKE J.L., van EIJK IZHAR C., SMULDERS YVO M., SERNE ERIK, DIJKMANS BEN A.C., van der HORST-BRUINSMA IRENE E., NURMOHAMED MICHAEL T. Signs of Accelerated Preclinical Atherosclerosis in Patients with Ankylosing Spondylitis. The Journal of Rheumatology. 2009;37(1):161&#x2013;166. doi: 10.3899/jrheum.090667.</Citation><ArticleIdList><ArticleId IdType="doi">10.3899/jrheum.090667</ArticleId><ArticleId IdType="pubmed">19955053</ArticleId></ArticleIdList></Reference><Reference><Citation>Gonzalez-Gay MA, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Martin J, Llorca J. Endothelial dysfunction, carotid intima-media thickness, and accelerated atherosclerosis in rheumatoid arthritis. Semin Arthritis Rheum. 2008;38(2):67&#x2013;70. doi: 10.1016/j.semarthrit.2008.02.001.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.semarthrit.2008.02.001</ArticleId><ArticleId IdType="pubmed">18395772</ArticleId></ArticleIdList></Reference><Reference><Citation>Bodnar N, Kerekes G, Seres I, Paragh G, Kappelmayer J, Nemethne ZG, Szegedi G, Shoenfeld Y, Sipka S, Soltesz P, et al. Assessment of subclinical vascular disease associated with ankylosing spondylitis. J Rheumatol. 2011;38(4):723&#x2013;729. doi: 10.3899/jrheum.100668.</Citation><ArticleIdList><ArticleId IdType="doi">10.3899/jrheum.100668</ArticleId><ArticleId IdType="pubmed">21239756</ArticleId></ArticleIdList></Reference><Reference><Citation>Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Dierssen T, Vaqueiro I, Blanco R, Martin J, Llorca J, Gonzalez-Gay MA. The high prevalence of subclinical atherosclerosis in patients with ankylosing spondylitis without clinically evident cardiovascular disease. Medicine (Baltimore) 2009;88(6):358&#x2013;365. doi: 10.1097/MD.0b013e3181c10773.</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/MD.0b013e3181c10773</ArticleId><ArticleId IdType="pubmed">19910750</ArticleId></ArticleIdList></Reference><Reference><Citation>Karampetsou MP, Liossis SN, Sfikakis PP. TNF-alpha antagonists beyond approved indications: stories of success and prospects for the future. QJM. 2010;103(12):917&#x2013;928. doi: 10.1093/qjmed/hcq152.</Citation><ArticleIdList><ArticleId IdType="doi">10.1093/qjmed/hcq152</ArticleId><ArticleId IdType="pubmed">20802008</ArticleId></ArticleIdList></Reference><Reference><Citation>Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet. 2007;370(9602):1861&#x2013;1874. doi: 10.1016/S0140-6736(07)60784-3.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0140-6736(07)60784-3</ArticleId><ArticleId IdType="pubmed">17570481</ArticleId></ArticleIdList></Reference><Reference><Citation>Verweij CL. Pharmacogenetics: anti-TNF therapy in RA--towards personalized medicine? Nat Rev Rheumatol. 2011;7(3):136&#x2013;138. doi: 10.1038/nrrheum.2011.13.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrrheum.2011.13</ArticleId><ArticleId IdType="pubmed">21304506</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Mesko B, Poliska S, Vancsa A, Szamosi S, Vegh E, Simkovics E, Laki J, Kurko J, Besenyei T, et al. Pharmacogenetics and pharmacogenomics in rheumatology. Immunol Res. 2013;56(2&#x2013;3):325&#x2013;333. doi: 10.1007/s12026-013-8405-z.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s12026-013-8405-z</ArticleId><ArticleId IdType="pmc">PMC4139282</ArticleId><ArticleId IdType="pubmed">23564183</ArticleId></ArticleIdList></Reference><Reference><Citation>Cronstein BN. Pharmacogenetics in the rheumatic diseases, from pret-a-porter to haute couture. Nat Clin Pract Rheumatol. 2006;2(1):2&#x2013;3. doi: 10.1038/ncprheum0072.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/ncprheum0072</ArticleId><ArticleId IdType="pubmed">16932642</ArticleId></ArticleIdList></Reference><Reference><Citation>Davila L, Ranganathan P. Pharmacogenetics: implications for therapy in rheumatic diseases. Nat Rev Rheumatol. 2011;7(9):537&#x2013;550. doi: 10.1038/nrrheum.2011.117.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/nrrheum.2011.117</ArticleId><ArticleId IdType="pubmed">21826093</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Szegedi A, Szekanecz Z, Palatka K, Papp M, Nagy L. Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets. BMC Med Genet. 2010;3:15.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2874757</ArticleId><ArticleId IdType="pubmed">20444268</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Nagy L. Gene expression profiles in peripheral blood for the diagnosis of autoimmune diseases. Trends Mol Med. 2011;17(4):223&#x2013;233. doi: 10.1016/j.molmed.2010.12.004.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.molmed.2010.12.004</ArticleId><ArticleId IdType="pubmed">21388884</ArticleId></ArticleIdList></Reference><Reference><Citation>Aziz H, Zaas A, Ginsburg GS. Peripheral blood gene expression profiling for cardiovascular disease assessment. Genomic Med. 2007;1(3&#x2013;4):105&#x2013;112. doi: 10.1007/s11568-008-9017-x.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s11568-008-9017-x</ArticleId><ArticleId IdType="pmc">PMC2269039</ArticleId><ArticleId IdType="pubmed">18923935</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Vancsa A, Szekanecz Z, Palatka K, Hollo Z, Horvath A, Steiner L, Zahuczky G, Podani J, et al. Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn&#x2019;s disease. Genome Med. 2013;5(6):59. doi: 10.1186/gm463.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/gm463</ArticleId><ArticleId IdType="pmc">PMC4064310</ArticleId><ArticleId IdType="pubmed">23809696</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Szamosi S, Szekanecz Z, Podani J, Varadi C, Guttman A, Nagy L. Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis. J Rheumatol. 2012;39(5):916&#x2013;928. doi: 10.3899/jrheum.110961.</Citation><ArticleIdList><ArticleId IdType="doi">10.3899/jrheum.110961</ArticleId><ArticleId IdType="pubmed">22467923</ArticleId></ArticleIdList></Reference><Reference><Citation>Kurko J, Besenyei T, Laki J, Glant TT, Mikecz K, Szekanecz Z. Genetics of rheumatoid arthritis - a comprehensive review. Clin Rev Allergy Immunol. 2013;45(2):170&#x2013;179. doi: 10.1007/s12016-012-8346-7.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s12016-012-8346-7</ArticleId><ArticleId IdType="pmc">PMC3655138</ArticleId><ArticleId IdType="pubmed">23288628</ArticleId></ArticleIdList></Reference><Reference><Citation>Lusis AJ. Genetics of atherosclerosis. Trends Genet. 2012;28(6):267&#x2013;275. doi: 10.1016/j.tig.2012.03.001.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.tig.2012.03.001</ArticleId><ArticleId IdType="pmc">PMC3362664</ArticleId><ArticleId IdType="pubmed">22480919</ArticleId></ArticleIdList></Reference><Reference><Citation>Marian AJ. The enigma of genetics etiology of atherosclerosis in the post-GWAS era. Curr Atheroscler Rep. 2012;14(4):295&#x2013;299. doi: 10.1007/s11883-012-0245-0.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s11883-012-0245-0</ArticleId><ArticleId IdType="pmc">PMC3389254</ArticleId><ArticleId IdType="pubmed">22437283</ArticleId></ArticleIdList></Reference><Reference><Citation>Farragher TM, Goodson NJ, Naseem H, Silman AJ, Thomson W, Symmons D, Barton A. Association of the HLA-DRB1 gene with premature death, particularly from cardiovascular disease, in patients with rheumatoid arthritis and inflammatory polyarthritis. Arthritis Rheum. 2008;58(2):359&#x2013;369. doi: 10.1002/art.23149.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.23149</ArticleId><ArticleId IdType="pmc">PMC3001034</ArticleId><ArticleId IdType="pubmed">18240242</ArticleId></ArticleIdList></Reference><Reference><Citation>Gonzalez-Gay MA, Gonzalez-Juanatey C, Lopez-Diaz MJ, Pineiro A, Garcia-Porrua C, Miranda-Filloy JA, Ollier WE, Martin J, Llorca J. HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis. Arthritis Rheum. 2007;57(1):125&#x2013;132. doi: 10.1002/art.22482.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.22482</ArticleId><ArticleId IdType="pubmed">17266100</ArticleId></ArticleIdList></Reference><Reference><Citation>Remuzgo-Martinez S, Genre F, Lopez-Mejias R, Ubilla B, Mijares V, Pina T, Corrales A, Blanco R, Martin J, Llorca J, et al. Expression of osteoprotegerin and its ligands, RANKL and TRAIL, in rheumatoid arthritis. Sci Rep. 2016;6:29713. doi: 10.1038/srep29713.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/srep29713</ArticleId><ArticleId IdType="pmc">PMC4940734</ArticleId><ArticleId IdType="pubmed">27403809</ArticleId></ArticleIdList></Reference><Reference><Citation>Lopez-Mejias R, Castaneda S, Gonzalez-Juanatey C, Corrales A, Ferraz-Amaro I, Genre F, Remuzgo-Martinez S, Rodriguez-Rodriguez L, Blanco R, Llorca J, et al. Cardiovascular risk assessment in patients with rheumatoid arthritis: the relevance of clinical, genetic and serological markers. Autoimmun Rev. 2016;15(11):1013&#x2013;1030. doi: 10.1016/j.autrev.2016.07.026.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.autrev.2016.07.026</ArticleId><ArticleId IdType="pubmed">27490206</ArticleId></ArticleIdList></Reference><Reference><Citation>Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569&#x2013;2581. doi: 10.1002/art.27584.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.27584</ArticleId><ArticleId IdType="pubmed">20872595</ArticleId></ArticleIdList></Reference><Reference><Citation>van Gestel AM, Prevoo ML, van 't Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum. 1996;39(1):34&#x2013;40. doi: 10.1002/art.1780390105.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.1780390105</ArticleId><ArticleId IdType="pubmed">8546736</ArticleId></ArticleIdList></Reference><Reference><Citation>Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39(2):257&#x2013;265. doi: 10.1016/S0735-1097(01)01746-6.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0735-1097(01)01746-6</ArticleId><ArticleId IdType="pubmed">11788217</ArticleId></ArticleIdList></Reference><Reference><Citation>Soltesz P, Der H, Kerekes G, Szodoray P, Szucs G, Danko K, Shoenfeld Y, Szegedi G, Szekanecz Z. A comparative study of arterial stiffness, flow-mediated vasodilation of the brachial artery, and the thickness of the carotid artery intima-media in patients with systemic autoimmune diseases. Clin Rheumatol. 2009;28(6):655&#x2013;662. doi: 10.1007/s10067-009-1118-y.</Citation><ArticleIdList><ArticleId IdType="doi">10.1007/s10067-009-1118-y</ArticleId><ArticleId IdType="pubmed">19224126</ArticleId></ArticleIdList></Reference><Reference><Citation>Kanters SD, Algra A, van Leeuwen MS, Banga JD. Reproducibility of in vivo carotid intima-media thickness measurements: a review. Stroke. 1997;28(3):665&#x2013;671. doi: 10.1161/01.STR.28.3.665.</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/01.STR.28.3.665</ArticleId><ArticleId IdType="pubmed">9056629</ArticleId></ArticleIdList></Reference><Reference><Citation>Baulmann J, Schillings U, Rickert S, Uen S, Dusing R, Illyes M, Cziraki A, Nickering G, Mengden T. A new oscillometric method for assessment of arterial stiffness: comparison with tonometric and piezo-electronic methods. J Hypertens. 2008;26(3):523&#x2013;528. doi: 10.1097/HJH.0b013e3282f314f7.</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/HJH.0b013e3282f314f7</ArticleId><ArticleId IdType="pubmed">18300864</ArticleId></ArticleIdList></Reference><Reference><Citation>Timar O, Soltesz P, Szamosi S, Der H, Szanto S, Szekanecz Z, Szucs G. Increased arterial stiffness as the marker of vascular involvement in systemic sclerosis. J Rheumatol. 2008;35(7):1329&#x2013;1333.</Citation><ArticleIdList><ArticleId IdType="pubmed">18484693</ArticleId></ArticleIdList></Reference><Reference><Citation>Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N, Jara LJ, Abu-Shakra M, Meroni PL, Sherer Y. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005;112(21):3337&#x2013;3347. doi: 10.1161/CIRCULATIONAHA.104.507996.</Citation><ArticleIdList><ArticleId IdType="doi">10.1161/CIRCULATIONAHA.104.507996</ArticleId><ArticleId IdType="pubmed">16301360</ArticleId></ArticleIdList></Reference><Reference><Citation>Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJ, Kvien TK, Dougados M, Radner H, Atzeni F, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76(1):17&#x2013;28. doi: 10.1136/annrheumdis-2016-209775.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/annrheumdis-2016-209775</ArticleId><ArticleId IdType="pubmed">27697765</ArticleId></ArticleIdList></Reference><Reference><Citation>de Vries R. Genetics of rheumatoid arthritis: time for a change! Curr Opin Rheumatol. 2011;23(3):227&#x2013;232. doi: 10.1097/BOR.0b013e3283457524.</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/BOR.0b013e3283457524</ArticleId><ArticleId IdType="pubmed">21427575</ArticleId></ArticleIdList></Reference><Reference><Citation>Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987;30(11):1205&#x2013;1213. doi: 10.1002/art.1780301102.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.1780301102</ArticleId><ArticleId IdType="pubmed">2446635</ArticleId></ArticleIdList></Reference><Reference><Citation>Schunkert H, Konig IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, Preuss M, Stewart AF, Barbalic M, Gieger C, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43(4):333&#x2013;338. doi: 10.1038/ng.784.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/ng.784</ArticleId><ArticleId IdType="pmc">PMC3119261</ArticleId><ArticleId IdType="pubmed">21378990</ArticleId></ArticleIdList></Reference><Reference><Citation>Gonzalez-Gay MA, Gonzalez-Juanatey C, Llorca J, Ollier WE, Martin J. Contribution of HLA-DRB1 shared epitope alleles and chronic inflammation to the increased incidence of cardiovascular disease in rheumatoid arthritis: comment on the article by Farragher et al. Arthritis Rheum. 2008;58(8):2584. doi: 10.1002/art.23637.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.23637</ArticleId><ArticleId IdType="pubmed">18668593</ArticleId></ArticleIdList></Reference><Reference><Citation>Garcia-Bermudez M, Lopez-Mejias R, Genre F, Castaneda S, Llorca J, Gonzalez-Juanatey C, Corrales A, Ubilla B, Miranda-Filloy JA, Pina T, et al. Interferon regulatory factor 5 genetic variants are associated with cardiovascular disease in patients with rheumatoid arthritis. Arthritis Res Ther. 2014;16(4):R146. doi: 10.1186/ar4608.</Citation><ArticleIdList><ArticleId IdType="doi">10.1186/ar4608</ArticleId><ArticleId IdType="pmc">PMC4227041</ArticleId><ArticleId IdType="pubmed">25011482</ArticleId></ArticleIdList></Reference><Reference><Citation>van Diepen JA, Jansen PA, Ballak DB, Hijmans A, Rutjes FP, Tack CJ, Netea MG, Schalkwijk J, Stienstra R. Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes. Sci Rep. 2016;6:21906. doi: 10.1038/srep21906.</Citation><ArticleIdList><ArticleId IdType="doi">10.1038/srep21906</ArticleId><ArticleId IdType="pmc">PMC4773925</ArticleId><ArticleId IdType="pubmed">26932716</ArticleId></ArticleIdList></Reference><Reference><Citation>Hu YW, Wu SG, Zhao JJ, Ma X, Lu JB, Xiu JC, Zhang Y, Huang C, Qiu YR, Sha YH, et al. VNN1 promotes atherosclerosis progression in apoE-/- mice fed a high-fat/high-cholesterol diet. J Lipid Res. 2016;57(8):1398&#x2013;1411. doi: 10.1194/jlr.M065565.</Citation><ArticleIdList><ArticleId IdType="doi">10.1194/jlr.M065565</ArticleId><ArticleId IdType="pmc">PMC4959856</ArticleId><ArticleId IdType="pubmed">27281478</ArticleId></ArticleIdList></Reference><Reference><Citation>Trysberg E, Nylen K, Rosengren LE, Tarkowski A. Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement. Arthritis Rheum. 2003;48(10):2881&#x2013;2887. doi: 10.1002/art.11279.</Citation><ArticleIdList><ArticleId IdType="doi">10.1002/art.11279</ArticleId><ArticleId IdType="pubmed">14558094</ArticleId></ArticleIdList></Reference><Reference><Citation>Gronblad M, Konttinen YT, Korkala O, Liesi P, Hukkanen M, Polak JM. Neuropeptides in synovium of patients with rheumatoid arthritis and osteoarthritis. J Rheumatol. 1988;15(12):1807&#x2013;1810.</Citation><ArticleIdList><ArticleId IdType="pubmed">3068364</ArticleId></ArticleIdList></Reference><Reference><Citation>Salih AM, Nixon NB, Dawes PT, Mattey DL. Prevalence of antibodies to neurofilament polypeptides in patients with rheumatoid arthritis complicated by peripheral neuropathy. Clin Exp Rheumatol. 1998;16(6):689&#x2013;694.</Citation><ArticleIdList><ArticleId IdType="pubmed">9844761</ArticleId></ArticleIdList></Reference><Reference><Citation>Kochunov P, Charlesworth J, Winkler A, Hong LE, Nichols TE, Curran JE, Sprooten E, Jahanshad N, Thompson PM, Johnson MP, et al. Transcriptomics of cortical gray matter thickness decline during normal aging. Neuroimage. 2013;82:273&#x2013;283. doi: 10.1016/j.neuroimage.2013.05.066.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.neuroimage.2013.05.066</ArticleId><ArticleId IdType="pmc">PMC3759649</ArticleId><ArticleId IdType="pubmed">23707588</ArticleId></ArticleIdList></Reference><Reference><Citation>Li N, Ma J, Li K, Guo C, Ming L. Different contributions of CDKAL1, KIF21B, and LRRK2/MUC19 polymorphisms to SAPHO syndrome, rheumatoid arthritis, ankylosing spondylitis, and seronegative spondyloarthropathy. Genet Test Mol Biomarkers. 2017;21(2):122&#x2013;126. doi: 10.1089/gtmb.2016.0112.</Citation><ArticleIdList><ArticleId IdType="doi">10.1089/gtmb.2016.0112</ArticleId><ArticleId IdType="pubmed">27936930</ArticleId></ArticleIdList></Reference><Reference><Citation>Dooley S, Herlitzka I, Hanselmann R, Ermis A, Henn W, Remberger K, Hopf T, Welter C. Constitutive expression of c-fos and c-jun, overexpression of ets-2, and reduced expression of metastasis suppressor gene nm23-H1 in rheumatoid arthritis. Ann Rheum Dis. 1996;55(5):298&#x2013;304. doi: 10.1136/ard.55.5.298.</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/ard.55.5.298</ArticleId><ArticleId IdType="pmc">PMC1010166</ArticleId><ArticleId IdType="pubmed">8660103</ArticleId></ArticleIdList></Reference><Reference><Citation>Sozen E, Karademir B, Yazgan B, Bozaykut P, Ozer NK. Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis. Redox Biol. 2014;2:732&#x2013;738. doi: 10.1016/j.redox.2014.02.007.</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.redox.2014.02.007</ArticleId><ArticleId IdType="pmc">PMC4085352</ArticleId><ArticleId IdType="pubmed">25009774</ArticleId></ArticleIdList></Reference><Reference><Citation>Han Z, Boyle DL, Aupperle KR, Bennett B, Manning AM, Firestein GS. Jun N-terminal kinase in rheumatoid arthritis. J Pharmacol Exp Ther. 1999;291(1):124&#x2013;130.</Citation><ArticleIdList><ArticleId IdType="pubmed">10490895</ArticleId></ArticleIdList></Reference><Reference><Citation>Kwok KHM, Cheng KKY, Hoo RLC, Ye D, Xu A, Lam KSL. Adipose-specific inactivation of JNK alleviates atherosclerosis in apoE-deficient mice. Clin Sci (Lond) 2016;130(22):2087&#x2013;2100. doi: 10.1042/CS20160465.</Citation><ArticleIdList><ArticleId IdType="doi">10.1042/CS20160465</ArticleId><ArticleId IdType="pubmed">27512097</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23653330</PMID><DateCompleted><Year>2013</Year><Month>09</Month><Day>04</Day></DateCompleted><DateRevised><Year>2022</Year><Month>06</Month><Day>01</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1529-0131</ISSN><JournalIssue CitedMedium="Internet"><Volume>65</Volume><Issue>7</Issue><PubDate><Year>2013</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Arthritis and rheumatism</Title><ISOAbbreviation>Arthritis Rheum</ISOAbbreviation></Journal><ArticleTitle>Differentially expressed epigenome modifiers, including aurora kinases A and B, in immune cells in rheumatoid arthritis in humans and mouse models.</ArticleTitle><Pagination><StartPage>1725</StartPage><EndPage>1735</EndPage><MedlinePgn>1725-35</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/art.37986</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To identify epigenetic factors that are implicated in the pathogenesis of rheumatoid arthritis (RA), and to explore the therapeutic potential of the targeted inhibition of these factors.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Polymerase chain reaction (PCR) arrays were used to investigate the expression profile of genes that encode key epigenetic regulator enzymes. Mononuclear cells from RA patients and mice were monitored for gene expression changes, in association with arthritis development in murine models of RA. Selected genes were further characterized by quantitative reverse transcription-PCR, Western blot, and flow cytometry methods. The targeted inhibition of the up-regulated enzymes was studied in arthritic mice.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">A set of genes with arthritis-specific expression was identified by the PCR arrays. Aurora kinases A and B, both of which were highly expressed in arthritic mice and treatment-naive RA patients, were selected for detailed analysis. Elevated aurora kinase expression was accompanied by increased phosphorylation of histone H3, which promotes proliferation of T lymphocytes. Treatment with VX-680, a pan-aurora kinase inhibitor, promoted B cell apoptosis, provided significant protection against disease onset, and attenuated inflammatory reactions in arthritic mice.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Arthritis development is accompanied by changes in expression of a number of epigenome-modifying enzymes. Drug-induced down-regulation of the aurora kinases, among other targets, seems to be sufficient to treat experimental arthritis. Development of new therapeutics that target aurora kinases can potentially improve RA management.</AbstractText><CopyrightInformation>Copyright &#xa9; 2013 by the American College of Rheumatology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Glant</LastName><ForeName>Tibor T</ForeName><Initials>TT</Initials><AffiliationInfo><Affiliation>Rush University Medical Center, Chicago, IL, USA. Tibor_Rauch@rush.edu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>K&#xe1;d&#xe1;r</LastName><ForeName>Andr&#xe1;s</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Kurk&#xf3;</LastName><ForeName>J&#xfa;lia</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Tryniszewska</LastName><ForeName>Beata</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>G&#xe1;l</LastName><ForeName>J&#xe1;nos</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>So&#xf3;s</LastName><ForeName>Gy&#xf6;rgyi</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Hoffmann</LastName><ForeName>Gyula</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Block</LastName><ForeName>Joel A</ForeName><Initials>JA</Initials></Author><Author ValidYN="Y"><LastName>Katz</LastName><ForeName>Robert S</ForeName><Initials>RS</Initials></Author><Author ValidYN="Y"><LastName>Mikecz</LastName><ForeName>Katalin</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Rauch</LastName><ForeName>Tibor A</ForeName><Initials>TA</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AR059356</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 AR064948</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR-059356</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Arthritis Rheum</MedlineTA><NlmUniqueID>0370605</NlmUniqueID><ISSNLinking>0004-3591</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D006657">Histones</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010879">Piperazines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047428">Protein Kinase Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>234335M86K</RegistryNumber><NameOfSubstance UI="C484810">tozasertib</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D064127">Aurora Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D017346">Protein Serine-Threonine Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001169" MajorTopicYN="N">Arthritis, Experimental</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention &amp; control</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D064127" MajorTopicYN="N">Aurora Kinases</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001402" MajorTopicYN="N">B-Lymphocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015153" MajorTopicYN="N">Blotting, Western</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D044127" MajorTopicYN="N">Epigenesis, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005434" MajorTopicYN="N">Flow Cytometry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020869" MajorTopicYN="N">Gene Expression Profiling</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006657" MajorTopicYN="N">Histones</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008811" MajorTopicYN="N">Mice, Inbred DBA</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010879" MajorTopicYN="N">Piperazines</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D047428" MajorTopicYN="N">Protein Kinase Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017346" MajorTopicYN="N">Protein Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists &amp; inhibitors</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020133" MajorTopicYN="N">Reverse Transcriptase Polymerase Chain Reaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013601" MajorTopicYN="N">T-Lymphocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015854" MajorTopicYN="N">Up-Regulation</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement><b>DISCLOSURE</b>. The authors declare no competing financial interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year><Month>6</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2013</Year><Month>4</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>5</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>5</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>9</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2014</Year><Month>7</Month><Day>17</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23653330</ArticleId><ArticleId IdType="mid">NIHMS557246</ArticleId><ArticleId IdType="pmc">PMC4102319</ArticleId><ArticleId IdType="doi">10.1002/art.37986</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Turesson C, O&#x2019;Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis. 2003;62:722&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1754626</ArticleId><ArticleId IdType="pubmed">12860726</ArticleId></ArticleIdList></Reference><Reference><Citation>Ballestar E. Epigenetic alterations in autoimmune rheumatic diseases. Nat Rev Rheumatol. 2011;7:263&#x2013;71.</Citation><ArticleIdList><ArticleId IdType="pubmed">21343899</ArticleId></ArticleIdList></Reference><Reference><Citation>Jacobi AM, Dorner T. Current aspects of anti-CD20 therapy in rheumatoid arthritis. Curr Opin Pharmacol. 2010;10:316&#x2013;21.</Citation><ArticleIdList><ArticleId IdType="pubmed">20189875</ArticleId></ArticleIdList></Reference><Reference><Citation>Chi P, Allis CD, Wang GG. Covalent histone modifications--miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer. 2010;10:457&#x2013;69.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3262678</ArticleId><ArticleId IdType="pubmed">20574448</ArticleId></ArticleIdList></Reference><Reference><Citation>Carmena M, Ruchaud S, Earnshaw WC. Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins. Curr Opin Cell Biol. 2009;21:796&#x2013;805.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2806521</ArticleId><ArticleId IdType="pubmed">19836940</ArticleId></ArticleIdList></Reference><Reference><Citation>Dar AA, Goff LW, Majid S, Berlin J, El-Rifai W. Aurora kinase inhibitors--rising stars in cancer therapeutics? Mol Cancer Ther. 2010;9:268&#x2013;78.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2820587</ArticleId><ArticleId IdType="pubmed">20124450</ArticleId></ArticleIdList></Reference><Reference><Citation>Crosio C, Fimia GM, Loury R, Kimura M, Okano Y, Zhou H, et al. Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Mol Cell Biol. 2002;22:874&#x2013;85.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC133550</ArticleId><ArticleId IdType="pubmed">11784863</ArticleId></ArticleIdList></Reference><Reference><Citation>Mikecz K, Glant TT, Poole AR. Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis Rheum. 1987;30:306&#x2013;18.</Citation><ArticleIdList><ArticleId IdType="pubmed">3566822</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Mikecz K. Proteoglycan aggrecan-induced arthritis: a murine autoimmune model of rheumatoid arthritis. Methods Mol Med. 2004;102:313&#x2013;38.</Citation><ArticleIdList><ArticleId IdType="pubmed">15286393</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Radacs M, Nagyeri G, Olasz K, Laszlo A, Boldizsar F, et al. Proteoglycan-induced arthritis and recombinant human proteoglycan aggrecan G1 domain-induced arthritis in BALB/c mice resembling two subtypes of rheumatoid arthritis. Arthritis Rheum. 2011;63:1312&#x2013;21.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3086933</ArticleId><ArticleId IdType="pubmed">21305522</ArticleId></ArticleIdList></Reference><Reference><Citation>Mikecz K, Brennan FR, Kim JH, Glant TT. Anti-CD44 treatment abrogates tissue oedema and leukocyte infiltration in murine arthritis. Nat Med. 1995;1:558&#x2013;63.</Citation><ArticleIdList><ArticleId IdType="pubmed">7585123</ArticleId></ArticleIdList></Reference><Reference><Citation>Adarichev VA, Valdez JC, Bardos T, Finnegan A, Mikecz K, Glant TT. Combined autoimmune models of arthritis reveal shared and independent qualitative (binary) and quantitative trait loci. J Immunol. 2003;170:2283&#x2013;92.</Citation><ArticleIdList><ArticleId IdType="pubmed">12594249</ArticleId></ArticleIdList></Reference><Reference><Citation>Myers LK, Seyer JM, Stuart JM, Kang AH. Suppression of murine collagen-induced arthritis by nasal administration of collagen. Immunology. 1997;90:161&#x2013;4.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1456748</ArticleId><ArticleId IdType="pubmed">9135541</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Adarichev VA, Nesterovitch AB, Szanto S, Oswald JP, Jacobs JJ, et al. Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis. Am J Med Sci. 2004;327(4):188&#x2013;95.</Citation><ArticleIdList><ArticleId IdType="pubmed">15084914</ArticleId></ArticleIdList></Reference><Reference><Citation>Yang D, Liu H, Goga A, Kim S, Yuneva M, Bishop JM. Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora-B kinase. Proc Natl Acad Sci U S A. 2010;107:13836&#x2013;41.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2922232</ArticleId><ArticleId IdType="pubmed">20643922</ArticleId></ArticleIdList></Reference><Reference><Citation>Taylor S, Wakem M, Dijkman G, Alsarraj M, Nguyen M. A practical approach to RT-qPCR-Publishing data that conform to the MIQE guidelines. Methods. 2010;50:S1&#x2013;S5.</Citation><ArticleIdList><ArticleId IdType="pubmed">20215014</ArticleId></ArticleIdList></Reference><Reference><Citation>Tate CM, Lee JH, Skalnik DG. CXXC finger protein 1 contains redundant functional domains that support embryonic stem cell cytosine methylation, histone methylation, and differentiation. Mol Cell Biol. 2009;29:3817&#x2013;31.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2704740</ArticleId><ArticleId IdType="pubmed">19433449</ArticleId></ArticleIdList></Reference><Reference><Citation>Boldizsar F, Kis-Toth K, Tarjanyi O, Olasz K, Hegyi A, Mikecz K, et al. Impaired activation-induced cell death promotes spontaneous arthritis in antigen (cartilage proteoglycan)-specific T cell receptor-transgenic mice. Arthritis Rheum. 2010;62(10):2984&#x2013;94.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2952044</ArticleId><ArticleId IdType="pubmed">20564001</ArticleId></ArticleIdList></Reference><Reference><Citation>Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69:1580&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">20699241</ArticleId></ArticleIdList></Reference><Reference><Citation>Beck IM, Vanden Berghe W, Vermeulen L, Bougarne N, Vander CB, Haegeman G, et al. Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-kappaB inhibition. EMBO J. 2008;27:1682&#x2013;93.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2435130</ArticleId><ArticleId IdType="pubmed">18511904</ArticleId></ArticleIdList></Reference><Reference><Citation>Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, et al. IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science. 1997;278:860&#x2013;6.</Citation><ArticleIdList><ArticleId IdType="pubmed">9346484</ArticleId></ArticleIdList></Reference><Reference><Citation>Angyal A, Egelston C, Kobezda T, Olasz K, Laszlo A, Glant TT, et al. Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody production, but does not involve significant influx of T cells into the joints. Arthritis Res Ther. 2010;12:R44.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2888192</ArticleId><ArticleId IdType="pubmed">20298547</ArticleId></ArticleIdList></Reference><Reference><Citation>Cantaert T, Kolln J, Timmer T, van der Pouw Kraan TC, Vandooren B, Thurlings RM, et al. B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis. J Immunol. 2008;181:785&#x2013;94.</Citation><ArticleIdList><ArticleId IdType="pubmed">18566445</ArticleId></ArticleIdList></Reference><Reference><Citation>Dorner T, Radbruch A, Burmester GR. B-cell-directed therapies for autoimmune disease. Nat Rev Rheumatol. 2009;5:433&#x2013;41.</Citation><ArticleIdList><ArticleId IdType="pubmed">19581902</ArticleId></ArticleIdList></Reference><Reference><Citation>Kotzin BL. The role of B cells in the pathogenesis of rheumatoid arthritis. J Rheumatol Suppl. 2005;73:14&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">15693111</ArticleId></ArticleIdList></Reference><Reference><Citation>Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med. 2004;10(3):262&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pubmed">14981513</ArticleId></ArticleIdList></Reference><Reference><Citation>Gizatullin F, Yao Y, Kung V, Harding MW, Loda M, Shapiro GI. The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function. Cancer Res. 2006;66(15):7668&#x2013;77.</Citation><ArticleIdList><ArticleId IdType="pubmed">16885368</ArticleId></ArticleIdList></Reference><Reference><Citation>Yu J, Wang Z, Kinzler KW, Vogelstein B, Zhang L. PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proc Natl Acad Sci U S A. 2003;100(4):1931&#x2013;6.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC149936</ArticleId><ArticleId IdType="pubmed">12574499</ArticleId></ArticleIdList></Reference><Reference><Citation>Karouzakis E, Gay RE, Gay S, Neidhart M. Epigenetic control in rheumatoid arthritis synovial fibroblasts. Nat Rev Rheumatol. 2009;5(5):266&#x2013;72.</Citation><ArticleIdList><ArticleId IdType="pubmed">19412193</ArticleId></ArticleIdList></Reference><Reference><Citation>Karouzakis E, Gay RE, Michel BA, Gay S, Neidhart M. DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 2009;60(12):3613&#x2013;22.</Citation><ArticleIdList><ArticleId IdType="pubmed">19950268</ArticleId></ArticleIdList></Reference><Reference><Citation>Huber LC, Brock M, Hemmatazad H, Giger OT, Moritz F, Trenkmann M, et al. Histone deacetylase/acetylase activity in total synovial tissue derived from rheumatoid arthritis and osteoarthritis patients. Arthritis Rheum. 2007;56(4):1087&#x2013;93.</Citation><ArticleIdList><ArticleId IdType="pubmed">17393417</ArticleId></ArticleIdList></Reference><Reference><Citation>Meinecke I, Cinski A, Baier A, Peters MA, Dankbar B, Wille A, et al. Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts. Proc Natl Acad Sci U S A. 2007;104(12):5073&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1829266</ArticleId><ArticleId IdType="pubmed">17360386</ArticleId></ArticleIdList></Reference><Reference><Citation>Ospelt C, Gay S. The role of resident synovial cells in destructive arthritis. Best Pract Res Clin Rheumatol. 2008;22(2):239&#x2013;52.</Citation><ArticleIdList><ArticleId IdType="pubmed">18455682</ArticleId></ArticleIdList></Reference><Reference><Citation>Wolter S, Doerrie A, Weber A, Schneider H, Hoffmann E, von der OJ, et al. c-Jun controls histone modifications, NF-kappaB recruitment, and RNA polymerase II function to activate the ccl2 gene. Mol Cell Biol. 2008;28:4407&#x2013;23.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2447141</ArticleId><ArticleId IdType="pubmed">18443042</ArticleId></ArticleIdList></Reference><Reference><Citation>Levy D, Kuo AJ, Chang Y, Schaefer U, Kitson C, Cheung P, et al. Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling. Nat Immunol. 2011;12(1):29&#x2013;36.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3074206</ArticleId><ArticleId IdType="pubmed">21131967</ArticleId></ArticleIdList></Reference><Reference><Citation>Levy D, Liu CL, Yang Z, Newman AM, Alizadeh AA, Utz PJ, et al. A proteomic approach for the identification of novel lysine methyltransferase substrates. Epigenetics Chromatin. 2011;4:19.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3212905</ArticleId><ArticleId IdType="pubmed">22024134</ArticleId></ArticleIdList></Reference><Reference><Citation>Villagra A, Cheng F, Wang HW, Suarez I, Glozak M, Maurin M, et al. The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nat Immunol. 2009;10:92&#x2013;100.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3925685</ArticleId><ArticleId IdType="pubmed">19011628</ArticleId></ArticleIdList></Reference><Reference><Citation>Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol. 2010;11:936&#x2013;44.</Citation><ArticleIdList><ArticleId IdType="pubmed">20729857</ArticleId></ArticleIdList></Reference><Reference><Citation>Jeon YJ, Lee KY, Cho YY, Pugliese A, Kim HG, Jeong CH, et al. Role of NEK6 in tumor promoter-induced transformation in JB6 C141 mouse skin epidermal cells. J Biol Chem. 2010;285:28126&#x2013;33.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2934677</ArticleId><ArticleId IdType="pubmed">20595392</ArticleId></ArticleIdList></Reference><Reference><Citation>Kishimoto T. IL-6: from its discovery to clinical applications. Int Immunol. 2010;22:347&#x2013;52.</Citation><ArticleIdList><ArticleId IdType="pubmed">20410258</ArticleId></ArticleIdList></Reference><Reference><Citation>Mori T, Miyamoto T, Yoshida H, Asakawa M, Kawasumi M, Kobayashi T, et al. IL-1beta and TNFalpha-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis. Int Immunol. 2011;23:701&#x2013;12.</Citation><ArticleIdList><ArticleId IdType="pubmed">21937456</ArticleId></ArticleIdList></Reference><Reference><Citation>Leandro MJ, Becerra-Fernandez E. B-cell therapies in established rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2011;25:535&#x2013;48.</Citation><ArticleIdList><ArticleId IdType="pubmed">22137923</ArticleId></ArticleIdList></Reference><Reference><Citation>Nakken B, Munthe LA, Konttinen YT, Sandberg AK, Szekanecz Z, Alex P, et al. B-cells and their targeting in rheumatoid arthritis--current concepts and future perspectives. Autoimmun Rev. 2011;11:28&#x2013;34.</Citation><ArticleIdList><ArticleId IdType="pubmed">21777703</ArticleId></ArticleIdList></Reference><Reference><Citation>Yazici Y. Long-term safety of methotrexate in the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2010;28:S65&#x2013;S67.</Citation><ArticleIdList><ArticleId IdType="pubmed">21044436</ArticleId></ArticleIdList></Reference><Reference><Citation>Albrecht K, Muller-Ladner U. Side effects and management of side effects of methotrexate in rheumatoid arthritis. Clin Exp Rheumatol. 2010;28:S95&#x2013;101.</Citation><ArticleIdList><ArticleId IdType="pubmed">21044440</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23564183</PMID><DateCompleted><Year>2014</Year><Month>01</Month><Day>24</Day></DateCompleted><DateRevised><Year>2022</Year><Month>03</Month><Day>10</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1559-0755</ISSN><JournalIssue CitedMedium="Internet"><Volume>56</Volume><Issue>2-3</Issue><PubDate><Year>2013</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Immunologic research</Title><ISOAbbreviation>Immunol Res</ISOAbbreviation></Journal><ArticleTitle>Pharmacogenetics and pharmacogenomics in rheumatology.</ArticleTitle><Pagination><StartPage>325</StartPage><EndPage>333</EndPage><MedlinePgn>325-33</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s12026-013-8405-z</ELocationID><Abstract><AbstractText>Pharmacogenetics and pharmacogenomics deal with possible associations of a single genetic polymorphism or those of multiple gene profiles with responses to drugs. In rheumatology, genes and gene signatures may be associated with altered efficacy and/or safety of anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs) and biologics. In brief, genes of cytochrome P450, other enzymes involved in drug metabolism, transporters and some cytokines have been associated with responses to and toxicity of non-steroidal anti-inflammatory drugs, corticosteroids and DMARDs. The efficacy of biologics may be related to alterations in cytokine, chemokine and Fc&#x3b3;R genes. Numerous studies reported multiple genetic signatures in association with responses to biologics; however, data are inconclusive. More, focused studies carried out in larger patient cohorts, using pre-selected genes, may be needed in order to determine the future of pharmacogenetics and pharmacogenomics as tools for personalized medicine in rheumatology.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Institute of Medicine, University of Debrecen Medical and Health Science Center, Nagyerdei Street 98, 4032, Debrecen, Hungary. szekanecz.zoltan@med.unideb.hu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mesk&#xf3;</LastName><ForeName>Bertalan</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Poliska</LastName><ForeName>Szilard</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>V&#xe1;ncsa</LastName><ForeName>Andrea</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Szamosi</LastName><ForeName>Szilvia</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>V&#xe9;gh</LastName><ForeName>Edit</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Simkovics</LastName><ForeName>Enik&#xf6;</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Laki</LastName><ForeName>Judit</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Kurk&#xf3;</LastName><ForeName>J&#xfa;lia</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Mikecz</LastName><ForeName>Katalin</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Glant</LastName><ForeName>Tibor T</ForeName><Initials>TT</Initials></Author><Author ValidYN="Y"><LastName>Nagy</LastName><ForeName>L&#xe1;szl&#xf3;</ForeName><Initials>L</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AR059356</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR064206</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Immunol Res</MedlineTA><NlmUniqueID>8611087</NlmUniqueID><ISSNLinking>0257-277X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018501">Antirheumatic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054316">Biomarkers, Pharmacological</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D026901">Membrane Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018121">Receptors, Cytokine</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017452">Receptors, IgG</NameOfSubstance></Chemical><Chemical><RegistryNumber>9035-51-2</RegistryNumber><NameOfSubstance UI="D003577">Cytochrome P-450 Enzyme System</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018501" MajorTopicYN="N">Antirheumatic Agents</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054316" MajorTopicYN="N">Biomarkers, Pharmacological</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001711" MajorTopicYN="N">Biotransformation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002986" MajorTopicYN="N">Clinical Trials as Topic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003577" MajorTopicYN="N">Cytochrome P-450 Enzyme System</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D026901" MajorTopicYN="N">Membrane Transport Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010597" MajorTopicYN="Y">Pharmacogenetics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020641" MajorTopicYN="N">Polymorphism, Single Nucleotide</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057285" MajorTopicYN="N">Precision Medicine</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018121" MajorTopicYN="N">Receptors, Cytokine</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017452" MajorTopicYN="N">Receptors, IgG</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012219" MajorTopicYN="N">Rheumatology</DescriptorName><QualifierName UI="Q000639" MajorTopicYN="N">trends</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059467" MajorTopicYN="N">Transcriptome</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>4</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>4</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>1</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2014</Year><Month>8</Month><Day>20</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23564183</ArticleId><ArticleId IdType="mid">NIHMS614609</ArticleId><ArticleId IdType="pmc">PMC4139282</ArticleId><ArticleId IdType="doi">10.1007/s12026-013-8405-z</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4(3):130&#x2013;6.</Citation><ArticleIdList><ArticleId IdType="pubmed">15823498</ArticleId></ArticleIdList></Reference><Reference><Citation>Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69(6):964&#x2013;75.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2935329</ArticleId><ArticleId IdType="pubmed">20444750</ArticleId></ArticleIdList></Reference><Reference><Citation>Raza K, Buckley CE, Salmon M, Buckley CD. Treating very early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2006;20(5):849&#x2013;63.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3145120</ArticleId><ArticleId IdType="pubmed">16980210</ArticleId></ArticleIdList></Reference><Reference><Citation>Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69:964&#x2013;75.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2935329</ArticleId><ArticleId IdType="pubmed">20444750</ArticleId></ArticleIdList></Reference><Reference><Citation>Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69(4):631&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3015099</ArticleId><ArticleId IdType="pubmed">20215140</ArticleId></ArticleIdList></Reference><Reference><Citation>Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">20699241</ArticleId></ArticleIdList></Reference><Reference><Citation>Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 69(6):964&#x2013;75.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2935329</ArticleId><ArticleId IdType="pubmed">20444750</ArticleId></ArticleIdList></Reference><Reference><Citation>Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, et al. American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis. 2011;70(3):404&#x2013;13.</Citation><ArticleIdList><ArticleId IdType="pubmed">21292833</ArticleId></ArticleIdList></Reference><Reference><Citation>de Vries RR, van der Woude D, Houwing JJ, Toes RE. Genetics of ACPA-positive rheumatoid arthritis: the beginning of the end? Ann Rheum Dis. 2011;70 (Suppl 1):i51&#x2013;4.</Citation><ArticleIdList><ArticleId IdType="pubmed">21339219</ArticleId></ArticleIdList></Reference><Reference><Citation>Szodoray P, Szabo Z, Kapitany A, Gyetvai A, Lakos G, Szanto S, et al. Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis. Autoimmun Rev. 2010;9(3):140&#x2013;3.</Citation><ArticleIdList><ArticleId IdType="pubmed">19427413</ArticleId></ArticleIdList></Reference><Reference><Citation>Daha NA, Toes RE. Rheumatoid arthritis: Are ACPA-positive and ACPA-negative RA the same disease? Nat Rev Rheumatol. 2011;7(4):202&#x2013;3.</Citation><ArticleIdList><ArticleId IdType="pubmed">21455249</ArticleId></ArticleIdList></Reference><Reference><Citation>Lundstrom E, Kallberg H, Smolnikova M, Ding B, Ronnelid J, Alfredsson L, et al. Opposing effects of HLA-DRB1*13 alleles on the risk of developing anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis. Arthritis Rheum. 2009;60(4):924&#x2013;30.</Citation><ArticleIdList><ArticleId IdType="pubmed">19333936</ArticleId></ArticleIdList></Reference><Reference><Citation>Laki J, Lundstrom E, Snir O, Ronnelid J, Ganji I, Catrina AI, et al. Very high levels of anti-citrullinated protein antibodies are associated with HLA-DRB1*15 non-shared epitope allele in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64(7):2078&#x2013;84.</Citation><ArticleIdList><ArticleId IdType="pubmed">22307773</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Helm-van Mil AH, Wesoly JZ, Huizinga TW. Understanding the genetic contribution to rheumatoid arthritis. Curr Opin Rheumatol. 2005;17(3):299&#x2013;304.</Citation><ArticleIdList><ArticleId IdType="pubmed">15838240</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Helm-van Mil AH, Toes RE, Huizinga TW. Genetic variants in the prediction of rheumatoid arthritis. Ann Rheum Dis. 2010;69(9):1694&#x2013;6.</Citation><ArticleIdList><ArticleId IdType="pubmed">20439292</ArticleId></ArticleIdList></Reference><Reference><Citation>Cronstein BN. Pharmacogenetics in the rheumatic diseases, from pret-a-porter to haute couture. Nat Clin Pract Rheumatol. 2006;2(1):2&#x2013;3.</Citation><ArticleIdList><ArticleId IdType="pubmed">16932642</ArticleId></ArticleIdList></Reference><Reference><Citation>Ranganathan P. Pharmacogenomics in rheumatoid arthritis. Methods Mol Biol. 2008;448:413&#x2013;35.</Citation><ArticleIdList><ArticleId IdType="pubmed">18370240</ArticleId></ArticleIdList></Reference><Reference><Citation>Davila L, Ranganathan P. Pharmacogenetics: implications for therapy in rheumatic diseases. Nat Rev Rheumatol. 2011;7(9):537&#x2013;50.</Citation><ArticleIdList><ArticleId IdType="pubmed">21826093</ArticleId></ArticleIdList></Reference><Reference><Citation>Verweij CL. Pharmacogenetics: Anti-TNF therapy in RA--towards personalized medicine? Nat Rev Rheumatol. 2011;7(3):136&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">21304506</ArticleId></ArticleIdList></Reference><Reference><Citation>Roses AD. Pharmacogenetics. Hum Mol Genet. 2001;10(20):2261&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pubmed">11673409</ArticleId></ArticleIdList></Reference><Reference><Citation>Emery P, Dorner T. Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response. Ann Rheum Dis. 2011;70(12):2063&#x2013;70.</Citation><ArticleIdList><ArticleId IdType="pubmed">22039166</ArticleId></ArticleIdList></Reference><Reference><Citation>Miossec P, Verweij CL, Klareskog L, Pitzalis C, Barton A, Lekkerkerker F, et al. Biomarkers and personalised medicine in rheumatoid arthritis: a proposal for interactions between academia, industry and regulatory bodies. Ann Rheum Dis. 2011;70(10):1713&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">21784723</ArticleId></ArticleIdList></Reference><Reference><Citation>Stamer UM, Zhang L, Stuber F. Personalized therapy in pain management: where do we stand? Pharmacogenomics. 2010;11(6):843&#x2013;64.</Citation><ArticleIdList><ArticleId IdType="pubmed">20504256</ArticleId></ArticleIdList></Reference><Reference><Citation>Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3(2):229&#x2013;43.</Citation><ArticleIdList><ArticleId IdType="pubmed">11972444</ArticleId></ArticleIdList></Reference><Reference><Citation>Xie HG, Prasad HC, Kim RB, Stein CM. CYP2C9 allelic variants: ethnic distribution and functional significance. Adv Drug Deliv Rev. 2002;54(10):1257&#x2013;70.</Citation><ArticleIdList><ArticleId IdType="pubmed">12406644</ArticleId></ArticleIdList></Reference><Reference><Citation>van Kalken CK, Broxterman HJ, Pinedo HM, Feller N, Dekker H, Lankelma J, et al. Cortisol is transported by the multidrug resistance gene product P-glycoprotein. Br J Cancer. 1993;67(2):284&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1968171</ArticleId><ArticleId IdType="pubmed">8094292</ArticleId></ArticleIdList></Reference><Reference><Citation>Daniel F, Loriot MA, Seksik P, Cosnes J, Gornet JM, Lemann M, et al. Multidrug resistance gene-1 polymorphisms and resistance to cyclosporine A in patients with steroid resistant ulcerative colitis. Inflamm Bowel Dis. 2007;13(1):19&#x2013;23.</Citation><ArticleIdList><ArticleId IdType="pubmed">17206635</ArticleId></ArticleIdList></Reference><Reference><Citation>Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000;97(7):3473&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC16264</ArticleId><ArticleId IdType="pubmed">10716719</ArticleId></ArticleIdList></Reference><Reference><Citation>Wasilewska A, Zalewski G, Chyczewski L, Zoch-Zwierz W. MDR-1 gene polymorphisms and clinical course of steroid-responsive nephrotic syndrome in children. Pediatr Nephrol. 2007;22(1):44&#x2013;51.</Citation><ArticleIdList><ArticleId IdType="pubmed">17043887</ArticleId></ArticleIdList></Reference><Reference><Citation>Borowski LC, Lopes RP, Gonzalez TP, Dummer LA, Chies JA, Silveira IG, et al. Is steroid resistance related to multidrug resistance-I (MDR-I) in rheumatoid arthritis? Int Immunopharmacol. 2007;7(6):836&#x2013;44.</Citation><ArticleIdList><ArticleId IdType="pubmed">17466917</ArticleId></ArticleIdList></Reference><Reference><Citation>Richaud-Patin Y, Vega-Boada F, Vidaller A, Llorente L. Multidrug resistance-1 (MDR-1) in autoimmune disorders IV. P-glycoprotein overfunction in lymphocytes from myasthenia gravis patients. Biomed Pharmacother. 2004;58(5):320&#x2013;4.</Citation><ArticleIdList><ArticleId IdType="pubmed">15194168</ArticleId></ArticleIdList></Reference><Reference><Citation>Llorente L, Richaud-Patin Y, Diaz-Borjon A, Alvarado de la Barrera C, Jakez-Ocampo J, de la Fuente H, et al. Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part I: Increased P-glycoprotein activity in lymphocytes from rheumatoid arthritis patients might influence disease outcome. Joint Bone Spine. 2000;67(1):30&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pubmed">10773966</ArticleId></ArticleIdList></Reference><Reference><Citation>Davila L, Ranganathan P. Pharmacogenetics: implications for therapy in rheumatic diseases. Nat Rev Rheumatol. 2011;7(9):537&#x2013;50.</Citation><ArticleIdList><ArticleId IdType="pubmed">21826093</ArticleId></ArticleIdList></Reference><Reference><Citation>Ulrich CM, Yasui Y, Storb R, Schubert MM, Wagner JL, Bigler J, et al. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood. 2001;98(1):231&#x2013;4.</Citation><ArticleIdList><ArticleId IdType="pubmed">11418485</ArticleId></ArticleIdList></Reference><Reference><Citation>Toffoli G, Veronesi A, Boiocchi M, Crivellari D. MTHFR gene polymorphism and severe toxicity during adjuvant treatment of early breast cancer with cyclophosphamide, methotrexate, and fluorouracil (CMF) Ann Oncol. 2000;11(3):373&#x2013;4.</Citation><ArticleIdList><ArticleId IdType="pubmed">10811509</ArticleId></ArticleIdList></Reference><Reference><Citation>van Ede AE, Laan RF, Blom HJ, Huizinga TW, Haagsma CJ, Giesendorf BA, et al. The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arthritis Rheum. 2001;44(11):2525&#x2013;30.</Citation><ArticleIdList><ArticleId IdType="pubmed">11710708</ArticleId></ArticleIdList></Reference><Reference><Citation>Lee YH, Song GG. Associations between the C677T and A1298C polymorphisms of MTHFR and the efficacy and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis. Clin Drug Investig. 2010;30(2):101&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">20067328</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Put NM, Gabreels F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet. 1998;62(5):1044&#x2013;51.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1377082</ArticleId><ArticleId IdType="pubmed">9545395</ArticleId></ArticleIdList></Reference><Reference><Citation>Berkun Y, Levartovsky D, Rubinow A, Orbach H, Aamar S, Grenader T, et al. Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. Ann Rheum Dis. 2004;63(10):1227&#x2013;31.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1754756</ArticleId><ArticleId IdType="pubmed">15361376</ArticleId></ArticleIdList></Reference><Reference><Citation>Kang SS, Wong PW, Zhou JM, Sora J, Lessick M, Ruggie N, et al. Thermolabile methylenetetrahydrofolate reductase in patients with coronary artery disease. Metabolism. 1988;37(7):611&#x2013;3.</Citation><ArticleIdList><ArticleId IdType="pubmed">3386531</ArticleId></ArticleIdList></Reference><Reference><Citation>Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet. 1988;43(4):414&#x2013;21.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1715503</ArticleId><ArticleId IdType="pubmed">3177384</ArticleId></ArticleIdList></Reference><Reference><Citation>Urano W, Taniguchi A, Yamanaka H, Tanaka E, Nakajima H, Matsuda Y, et al. Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses. Pharmacogenetics. 2002;12(3):183&#x2013;90.</Citation><ArticleIdList><ArticleId IdType="pubmed">11927833</ArticleId></ArticleIdList></Reference><Reference><Citation>De Mattia E, Toffoli G. C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation. Eur J Cancer. 2009;45(8):1333&#x2013;51.</Citation><ArticleIdList><ArticleId IdType="pubmed">19144510</ArticleId></ArticleIdList></Reference><Reference><Citation>Friedman G, Goldschmidt N, Friedlander Y, Ben-Yehuda A, Selhub J, Babaey S, et al. A common mutation A1298C in human methylenetetrahydrofolate reductase gene: association with plasma total homocysteine and folate concentrations. J Nutr. 1999;129(9):1656&#x2013;61.</Citation><ArticleIdList><ArticleId IdType="pubmed">10460200</ArticleId></ArticleIdList></Reference><Reference><Citation>Palomino-Morales R, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Rodriguez L, Miranda-Filloy JA, Fernandez-Gutierrez B, et al. A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid arthritis. Arthritis Res Ther. 2010;12(2):R71.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2888227</ArticleId><ArticleId IdType="pubmed">20423475</ArticleId></ArticleIdList></Reference><Reference><Citation>Rothem L, Aronheim A, Assaraf YG. Alterations in the expression of transcription factors and the reduced folate carrier as a novel mechanism of antifolate resistance in human leukemia cells. J Biol Chem. 2003;278(11):8935&#x2013;41.</Citation><ArticleIdList><ArticleId IdType="pubmed">12519783</ArticleId></ArticleIdList></Reference><Reference><Citation>Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004;50(9):2766&#x2013;74.</Citation><ArticleIdList><ArticleId IdType="pubmed">15457444</ArticleId></ArticleIdList></Reference><Reference><Citation>Dervieux T, Kremer J, Lein DO, Capps R, Barham R, Meyer G, et al. Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis. Pharmacogenetics. 2004;14(11):733&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pubmed">15564880</ArticleId></ArticleIdList></Reference><Reference><Citation>Pawlik A, Wrzesniewska J, Fiedorowicz-Fabrycy I, Gawronska-Szklarz B. The MDR1 3435 polymorphism in patients with rheumatoid arthritis. Int J Clin Pharmacol Ther. 2004;42(9):496&#x2013;503.</Citation><ArticleIdList><ArticleId IdType="pubmed">15487808</ArticleId></ArticleIdList></Reference><Reference><Citation>Horie N, Aiba H, Oguro K, Hojo H, Takeishi K. Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5&#x2032;-terminal regulatory region of the human gene for thymidylate synthase. Cell Struct Funct. 1995;20(3):191&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pubmed">7586009</ArticleId></ArticleIdList></Reference><Reference><Citation>Ranganathan P, Culverhouse R, Marsh S, Mody A, Scott-Horton TJ, Brasington R, et al. Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasian and African American patients with rheumatoid arthritis. J Rheumatol. 2008;35(4):572&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pubmed">18381794</ArticleId></ArticleIdList></Reference><Reference><Citation>Kumagai K, Hiyama K, Oyama T, Maeda H, Kohno N. Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis. Int J Mol Med. 2003;11(5):593&#x2013;600.</Citation><ArticleIdList><ArticleId IdType="pubmed">12684695</ArticleId></ArticleIdList></Reference><Reference><Citation>Takatori R, Takahashi KA, Tokunaga D, Hojo T, Fujioka M, Asano T, et al. ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients. Clin Exp Rheumatol. 2006;24(5):546&#x2013;54.</Citation><ArticleIdList><ArticleId IdType="pubmed">17181924</ArticleId></ArticleIdList></Reference><Reference><Citation>Dervieux T, Furst D, Lein DO, Capps R, Smith K, Caldwell J, et al. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis. 2005;64(8):1180&#x2013;5.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1755602</ArticleId><ArticleId IdType="pubmed">15677700</ArticleId></ArticleIdList></Reference><Reference><Citation>Tolusso B, Pietrapertosa D, Morelli A, De Santis M, Gremese E, Farina G, et al. IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein plasma levels and response to therapy. Pharmacogenomics. 2006;7(5):683&#x2013;95.</Citation><ArticleIdList><ArticleId IdType="pubmed">16886894</ArticleId></ArticleIdList></Reference><Reference><Citation>Kumagai S, Komada F, Kita T, Morinobu A, Ozaki S, Ishida H, et al. N-acetyltransferase 2 genotype-related efficacy of sulfasalazine in patients with rheumatoid arthritis. Pharm Res. 2004;21(2):324&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pubmed">15032315</ArticleId></ArticleIdList></Reference><Reference><Citation>Tanaka E, Taniguchi A, Urano W, Nakajima H, Matsuda Y, Kitamura Y, et al. Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene. J Rheumatol. 2002;29(12):2492&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pubmed">12465141</ArticleId></ArticleIdList></Reference><Reference><Citation>Cohen SB, Iqbal I. Leflunomide. Int J Clin Pract. 2003;57(2):115&#x2013;20.</Citation><ArticleIdList><ArticleId IdType="pubmed">12661795</ArticleId></ArticleIdList></Reference><Reference><Citation>Lennard L, Van Loon JA, Weinshilboum RM. Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther. 1989;46(2):149&#x2013;54.</Citation><ArticleIdList><ArticleId IdType="pubmed">2758725</ArticleId></ArticleIdList></Reference><Reference><Citation>Lennard L, Lilleyman JS. Individualizing therapy with 6-mercaptopurine and 6-thioguanine related to the thiopurine methyltransferase genetic polymorphism. Ther Drug Monit. 1996;18(4):328&#x2013;34.</Citation><ArticleIdList><ArticleId IdType="pubmed">8857546</ArticleId></ArticleIdList></Reference><Reference><Citation>Clunie GP, Lennard L. Relevance of thiopurine methyltransferase status in rheumatology patients receiving azathioprine. Rheumatology (Oxford) 2004;43(1):13&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">14566029</ArticleId></ArticleIdList></Reference><Reference><Citation>Bonhomme-Faivre L, Devocelle A, Saliba F, Chatled S, Maccario J, Farinotti R, et al. MDR-1 C3435T polymorphism influences cyclosporine a dose requirement in liver-transplant recipients. Transplantation. 2004;78(1):21&#x2013;5.</Citation><ArticleIdList><ArticleId IdType="pubmed">15257034</ArticleId></ArticleIdList></Reference><Reference><Citation>van Vollenhoven RF. Switching between anti-tumour necrosis factors: trying to get a handle on a complex issue. Ann Rheum Dis. 2007;66(7):849&#x2013;51.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1955116</ArticleId><ArticleId IdType="pubmed">17576784</ArticleId></ArticleIdList></Reference><Reference><Citation>Radstake TR, Petit E, Pierlot C, van de Putte LB, Cornelis F, Barrera P. Role of Fcgamma receptors IIA, IIIA, and IIIB in susceptibility to rheumatoid arthritis. J Rheumatol. 2003;30(5):926&#x2013;33.</Citation><ArticleIdList><ArticleId IdType="pubmed">12734884</ArticleId></ArticleIdList></Reference><Reference><Citation>Sfar I, Dhaouadi T, Habibi I, Abdelmoula L, Makhlouf M, Ben Romdhane T, et al. Functional polymorphisms of PTPN22 and FcgR genes in Tunisian patients with rheumatoid arthritis. Arch Inst Pasteur Tunis. 2009;86(1&#x2013;4):51&#x2013;62.</Citation><ArticleIdList><ArticleId IdType="pubmed">20707220</ArticleId></ArticleIdList></Reference><Reference><Citation>Tutuncu Z, Kavanaugh A, Zvaifler N, Corr M, Deutsch R, Boyle D. Fcgamma receptor type IIIA polymorphisms influence treatment outcomes in patients with inflammatory arthritis treated with tumor necrosis factor alpha-blocking agents. Arthritis Rheum. 2005;52(9):2693&#x2013;6.</Citation><ArticleIdList><ArticleId IdType="pubmed">16142749</ArticleId></ArticleIdList></Reference><Reference><Citation>Coulthard LR, Taylor JC, Eyre S, Robinson JI, Wilson AG, Isaacs JD, et al. Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients. Ann Rheum Dis. 2010;70(1):98&#x2013;103.</Citation><ArticleIdList><ArticleId IdType="pubmed">20805296</ArticleId></ArticleIdList></Reference><Reference><Citation>Ruyssen-Witrand A, Rouanet S, Combe B, Dougados M, Le Loet X, Sibilia J, et al. Fcgamma receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. 2012;71(6):875&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pubmed">22368231</ArticleId></ArticleIdList></Reference><Reference><Citation>Fabris M, Quartuccio L, Lombardi S, Saracco M, Atzeni F, Carletto A, et al. The CC homozygosis of the &#x2212;174G&gt;C IL-6 polymorphism predicts a lower efficacy of rituximab therapy in rheumatoid arthritis. Autoimmun Rev. 2010;11(5):315&#x2013;20.</Citation><ArticleIdList><ArticleId IdType="pubmed">20974296</ArticleId></ArticleIdList></Reference><Reference><Citation>Gragnani L, Piluso A, Giannini C, Caini P, Fognani E, Monti M, et al. Genetic determinants in hepatitis C virus-associated mixed cryoglobulinemia: role of polymorphic variants of BAFF promoter and Fcgamma receptors. Arthritis Rheum. 2011;63(5):1446&#x2013;51.</Citation><ArticleIdList><ArticleId IdType="pubmed">21538321</ArticleId></ArticleIdList></Reference><Reference><Citation>Danila MI, Hughes LB, Bridges SL. Pharmacogenetics of etanercept in rheumatoid arthritis. Pharmacogenomics. 2008;9(8):1011&#x2013;5.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3746504</ArticleId><ArticleId IdType="pubmed">18681777</ArticleId></ArticleIdList></Reference><Reference><Citation>Koczan D, Drynda S, Hecker M, Drynda A, Guthke R, Kekow J, et al. Molecular discrimination of responders and nonresponders to anti-TNF alpha therapy in rheumatoid arthritis by etanercept. Arthritis Res Ther. 2008;10(3):R50.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2483439</ArticleId><ArticleId IdType="pubmed">18454843</ArticleId></ArticleIdList></Reference><Reference><Citation>Padyukov L, Lampa J, Heimburger M, Ernestam S, Cederholm T, Lundkvist I, et al. Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis. Ann Rheum Dis. 2003;62(6):526&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1754569</ArticleId><ArticleId IdType="pubmed">12759288</ArticleId></ArticleIdList></Reference><Reference><Citation>Julia A, Erra A, Palacio C, Tomas C, Sans X, Barcelo P, et al. An eight-gene blood expression profile predicts the response to infliximab in rheumatoid arthritis. PLoS ONE. 2009;4(10):e7556.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2762038</ArticleId><ArticleId IdType="pubmed">19847310</ArticleId></ArticleIdList></Reference><Reference><Citation>Lequerre T, Gauthier-Jauneau AC, Bansard C, Derambure C, Hiron M, Vittecoq O, et al. Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis. Arthritis Res Ther. 2006;8(4):R105.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1779405</ArticleId><ArticleId IdType="pubmed">16817978</ArticleId></ArticleIdList></Reference><Reference><Citation>Sekiguchi N, Kawauchi S, Furuya T, Inaba N, Matsuda K, Ando S, et al. Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-alpha monoclonal antibody, infliximab. Rheumatology (Oxford) 2008;47(6):780&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">18388148</ArticleId></ArticleIdList></Reference><Reference><Citation>Mugnier B, Balandraud N, Darque A, Roudier C, Roudier J, Reviron D. Polymorphism at position &#x2212;308 of the tumor necrosis factor alpha gene influences outcome of infliximab therapy in rheumatoid arthritis. Arthritis Rheum. 2003;48(7):1849&#x2013;52.</Citation><ArticleIdList><ArticleId IdType="pubmed">12847678</ArticleId></ArticleIdList></Reference><Reference><Citation>Plant D, Bowes J, Potter C, Hyrich KL, Morgan AW, Wilson AG, et al. Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci. Arthritis Rheum. 2011;63(3):645&#x2013;53.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3084508</ArticleId><ArticleId IdType="pubmed">21061259</ArticleId></ArticleIdList></Reference><Reference><Citation>Verweij CL. Pharmacogenetics: Anti-TNF therapy in RA--towards personalized medicine? Nat Rev Rheumatol. 2011;7(3):136&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">21304506</ArticleId></ArticleIdList></Reference><Reference><Citation>Coulthard LR, Taylor JC, Eyre S, Robinson JI, Wilson AG, Isaacs JD, et al. Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients. Ann Rheum Dis. 2011;70(1):98&#x2013;103.</Citation><ArticleIdList><ArticleId IdType="pubmed">20805296</ArticleId></ArticleIdList></Reference><Reference><Citation>Potter C, Cordell HJ, Barton A, Daly AK, Hyrich KL, Mann DA, et al. Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NF{kappa}B signalling pathways. Ann Rheum Dis. 2010;69(7):1315&#x2013;20.</Citation><ArticleIdList><ArticleId IdType="pubmed">20448286</ArticleId></ArticleIdList></Reference><Reference><Citation>Potter C, Hyrich KL, Tracey A, Lunt M, Plant D, Symmons DP, et al. Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis. Ann Rheum Dis. 2009;68(1):69&#x2013;74.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2596303</ArticleId><ArticleId IdType="pubmed">18375541</ArticleId></ArticleIdList></Reference><Reference><Citation>Raterman HG, Vosslamber S, de Ridder S, Nurmohamed MT, Lems WF, Boers M, et al. The interferon type I signature towards prediction of non-response to rituximab in rheumatoid arthritis patients. Arthritis Res Ther. 2012;14(2):R95.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3446469</ArticleId><ArticleId IdType="pubmed">22540992</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Szamosi S, Szekanecz Z, Podani J, Varadi C, et al. Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis. J Rheumatol. 2012;39(5):916&#x2013;28.</Citation><ArticleIdList><ArticleId IdType="pubmed">22467923</ArticleId></ArticleIdList></Reference><Reference><Citation>Mattey DL, Brownfield A, Dawes PT. Relationship between pack-year history of smoking and response to tumor necrosis factor antagonists in patients with rheumatoid arthritis. J Rheumatol. 2009;36(6):1180&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pubmed">19447930</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Nagy L. Gene expression profiles in peripheral blood for the diagnosis of autoimmune diseases. Trends Mol Med. 2011;17(4):223&#x2013;33.</Citation><ArticleIdList><ArticleId IdType="pubmed">21388884</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Szegedi A, Szekanecz Z, Palatka K, Papp M, et al. Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets. BMC Med Genomics. 2010;3:15.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2874757</ArticleId><ArticleId IdType="pubmed">20444268</ArticleId></ArticleIdList></Reference><Reference><Citation>Marsal S, Julia A. Rheumatoid arthritis pharmacogenomics. Pharmacogenomics. 2010;11(5):617&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pubmed">20415547</ArticleId></ArticleIdList></Reference><Reference><Citation>Filkova M, Jungel A, Gay RE, Gay S. MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. BioDrugs. 2012;26(3):131&#x2013;41.</Citation><ArticleIdList><ArticleId IdType="pubmed">22494429</ArticleId></ArticleIdList></Reference><Reference><Citation>Tzvetkov M, von Ahsen N. Pharmacogenetic screening for drug therapy: from single gene markers to decision making in the next generation sequencing era. Pathology. 2012;44(2):166&#x2013;80.</Citation><ArticleIdList><ArticleId IdType="pubmed">22228255</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23288628</PMID><DateCompleted><Year>2014</Year><Month>03</Month><Day>31</Day></DateCompleted><DateRevised><Year>2022</Year><Month>04</Month><Day>09</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1559-0267</ISSN><JournalIssue CitedMedium="Internet"><Volume>45</Volume><Issue>2</Issue><PubDate><Year>2013</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Clinical reviews in allergy &amp; immunology</Title><ISOAbbreviation>Clin Rev Allergy Immunol</ISOAbbreviation></Journal><ArticleTitle>Genetics of rheumatoid arthritis - a comprehensive review.</ArticleTitle><Pagination><StartPage>170</StartPage><EndPage>179</EndPage><MedlinePgn>170-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s12016-012-8346-7</ELocationID><Abstract><AbstractText>The "Bermuda triangle" of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11-37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci - Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively - have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kurk&#xf3;</LastName><ForeName>J&#xfa;lia</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Institute of Medicine, University of Debrecen Medical and Health Science Center, Nagyerdei str 98, Debrecen, 4032, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Laki</LastName><ForeName>Judit</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Glant</LastName><ForeName>Tibor T</ForeName><Initials>TT</Initials></Author><Author ValidYN="Y"><LastName>Mikecz</LastName><ForeName>Katalin</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AR059356</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Clin Rev Allergy Immunol</MedlineTA><NlmUniqueID>9504368</NlmUniqueID><ISSNLinking>1080-0549</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D006680">HLA Antigens</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C515500">IL23R protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018123">Receptors, Interleukin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047990">TNF Receptor-Associated Factor 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.3.48</RegistryNumber><NameOfSubstance UI="C516765">PTPN22 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.3.48</RegistryNumber><NameOfSubstance UI="D054596">Protein Tyrosine Phosphatase, Non-Receptor Type 22</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059647" MajorTopicYN="N">Gene-Environment Interaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055106" MajorTopicYN="N">Genome-Wide Association Study</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006680" MajorTopicYN="N">HLA Antigens</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011110" MajorTopicYN="N">Polymorphism, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054596" MajorTopicYN="N">Protein Tyrosine Phosphatase, Non-Receptor Type 22</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018123" MajorTopicYN="N">Receptors, Interleukin</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012907" MajorTopicYN="N">Smoking</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D047990" MajorTopicYN="N">TNF Receptor-Associated Factor 1</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>1</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2013</Year><Month>1</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>4</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2013</Year><Month>10</Month><Day>1</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23288628</ArticleId><ArticleId IdType="mid">NIHMS440178</ArticleId><ArticleId IdType="pmc">PMC3655138</ArticleId><ArticleId IdType="doi">10.1007/s12016-012-8346-7</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005;4(3):130&#x2013;136.</Citation><ArticleIdList><ArticleId IdType="pubmed">15823498</ArticleId></ArticleIdList></Reference><Reference><Citation>Klareskog L, Padyukov L, Alfredsson L. Smoking as a trigger for inflammatory rheumatic diseases. Curr Opin Rheumatol. 2007;19(1):49&#x2013;54.</Citation><ArticleIdList><ArticleId IdType="pubmed">17143096</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Helm-van Mil AH, Wesoly JZ, Huizinga TW. Understanding the genetic contribution to rheumatoid arthritis. Curr Opin Rheumatol. 2005;17(3):299&#x2013;304.</Citation><ArticleIdList><ArticleId IdType="pubmed">15838240</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Woude D, Alemayehu WG, Verduijn W, de Vries RR, Houwing-Duistermaat JJ, Huizinga TW, et al. Gene&#x2013;environment interaction influences the reactivity of autoantibodies to citrullinated antigens in rheumatoid arthritis. Nat Genet. 2010;42(10):814&#x2013;816. author reply 816.</Citation><ArticleIdList><ArticleId IdType="pubmed">20877316</ArticleId></ArticleIdList></Reference><Reference><Citation>Szodoray P, Szabo Z, Kapitany A, Gyetvai A, Lakos G, Szanto S, et al. Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis. Autoimmun Rev. 2010;9(3):140&#x2013;143.</Citation><ArticleIdList><ArticleId IdType="pubmed">19427413</ArticleId></ArticleIdList></Reference><Reference><Citation>de Vries R. Genetics of rheumatoid arthritis: time for a change! Curr Opin Rheumatol. 2011;23(3):227&#x2013;232.</Citation><ArticleIdList><ArticleId IdType="pubmed">21427575</ArticleId></ArticleIdList></Reference><Reference><Citation>Cooles FA, Isaacs JD. Pathophysiology of rheumatoid arthritis. Curr Opin Rheumatol. 23(3):233&#x2013;240.</Citation><ArticleIdList><ArticleId IdType="pubmed">21427580</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Soos L, Szabo Z, Fekete A, Kapitany A, Vegvari A, et al. Anti-citrullinated protein antibodies in rheumatoid arthritis: as good as it gets? Clin Rev Allergy Immunol. 2008;34(1):26&#x2013;31.</Citation><ArticleIdList><ArticleId IdType="pubmed">18270854</ArticleId></ArticleIdList></Reference><Reference><Citation>Klareskog L, Padyukov L, Lorentzen J, Alfredsson L. Mechanisms of disease: genetic susceptibility and environmental triggers in the development of rheumatoid arthritis. Nat Clin Pract Rheumatol. 2006;2(8):425&#x2013;433.</Citation><ArticleIdList><ArticleId IdType="pubmed">16932734</ArticleId></ArticleIdList></Reference><Reference><Citation>Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L. A gene&#x2013;environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 2004;50(10):3085&#x2013;3092.</Citation><ArticleIdList><ArticleId IdType="pubmed">15476204</ArticleId></ArticleIdList></Reference><Reference><Citation>Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69(6):964&#x2013;975.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2935329</ArticleId><ArticleId IdType="pubmed">20444750</ArticleId></ArticleIdList></Reference><Reference><Citation>MacGregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Aho K, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 2000;43(1):30&#x2013;37.</Citation><ArticleIdList><ArticleId IdType="pubmed">10643697</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Szegedi A, Szekanecz Z, Palatka K, Papp M, et al. Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets. BMC Med Genomics. 2010;3:15.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2874757</ArticleId><ArticleId IdType="pubmed">20444268</ArticleId></ArticleIdList></Reference><Reference><Citation>Lee HS, Irigoyen P, Kern M, Lee A, Batliwalla F, Khalili H, et al. Interaction between smoking, the shared epitope, and anti-cyclic citrullinated peptide: a mixed picture in three large North American rheumatoid arthritis cohorts. Arthritis Rheum. 2007;56(6):1745&#x2013;1753.</Citation><ArticleIdList><ArticleId IdType="pubmed">17530703</ArticleId></ArticleIdList></Reference><Reference><Citation>Kapitany A, Szabo Z, Lakos G, Aleksza M, Vegvari A, Soos L, et al. Associations between serum anti-CCP antibody, rheumatoid factor levels and HLA-DR4 expression in Hungarian patients with rheumatoid arthritis. Isr Med Assoc J. 2008;10(1):32&#x2013;36.</Citation><ArticleIdList><ArticleId IdType="pubmed">18300568</ArticleId></ArticleIdList></Reference><Reference><Citation>Besenyei T, Gyetvai A, Szabo Z, Fekete A, Kapitany A, Szodoray P, et al. Associations of HLA-shared epitope, anti-citrullinated peptide antibodies and lifestyle-related factors in Hungarian patients with rheumatoid arthritis: data from the first Central-Eastern European cohort. Joint Bone Spine. 2011;78(6):652&#x2013;653.</Citation><ArticleIdList><ArticleId IdType="pubmed">21733730</ArticleId></ArticleIdList></Reference><Reference><Citation>Scott IC, Steer S, Lewis CM, Cope AP. Precipitating and perpetuating factors of rheumatoid arthritis immunopathology: linking the triad of genetic predisposition, environmental risk factors and autoimmunity to disease pathogenesis. Best Pract Res Clin Rheumatol. 2011;25(4):447&#x2013;468.</Citation><ArticleIdList><ArticleId IdType="pubmed">22137917</ArticleId></ArticleIdList></Reference><Reference><Citation>Vittecoq O, Lequerre T, Goeb V, Le Loet X, Abdesselam TA, Klemmer N. Smoking and inflammatory diseases. Best Pract Res Clin Rheumatol. 2008;22(5):923&#x2013;935.</Citation><ArticleIdList><ArticleId IdType="pubmed">19028372</ArticleId></ArticleIdList></Reference><Reference><Citation>Davila L, Ranganathan P. Pharmacogenetics: implications for therapy in rheumatic diseases. Nat Rev Rheumatol. 2011;7(9):537&#x2013;550.</Citation><ArticleIdList><ArticleId IdType="pubmed">21826093</ArticleId></ArticleIdList></Reference><Reference><Citation>Cronstein BN. Pharmacogenetics in the rheumatic diseases, from pret-a-porter to haute couture. Nat Clin Pract Rheumatol. 2006;2(1):2&#x2013;3.</Citation><ArticleIdList><ArticleId IdType="pubmed">16932642</ArticleId></ArticleIdList></Reference><Reference><Citation>Danila MI, Hughes LB, Bridges SL. Pharmacogenetics of etanercept in rheumatoid arthritis. Pharmacogenomics. 2008;9(8):1011&#x2013;1015.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3746504</ArticleId><ArticleId IdType="pubmed">18681777</ArticleId></ArticleIdList></Reference><Reference><Citation>Mesko B, Poliska S, Szamosi S, Szekanecz Z, Podani J, Varadi C, et al. Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis. J Rheumatol. 2012;39(5):916&#x2013;928.</Citation><ArticleIdList><ArticleId IdType="pubmed">22467923</ArticleId></ArticleIdList></Reference><Reference><Citation>Plant D, Bowes J, Potter C, Hyrich KL, Morgan AW, Wilson AG, et al. Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci. Arthritis Rheum. 2011;63(3):645&#x2013;653.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3084508</ArticleId><ArticleId IdType="pubmed">21061259</ArticleId></ArticleIdList></Reference><Reference><Citation>Centola M, Szekanecz Z, Kiss E, Zeher M, Szegedi G, Nakken B, et al. Gene expression profiles of systemic lupus erythematosus and rheumatoid arthritis. Expert Rev Clin Immunol. 2007;3(5):797&#x2013;806.</Citation><ArticleIdList><ArticleId IdType="pubmed">20477029</ArticleId></ArticleIdList></Reference><Reference><Citation>Feng T, Zhu X. Genome-wide searching of rare genetic variants in WTCCC data. Hum Genet. 2010;128(3):269&#x2013;280.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2922446</ArticleId><ArticleId IdType="pubmed">20549515</ArticleId></ArticleIdList></Reference><Reference><Citation>Craddock N, Hurles ME, Cardin N, Pearson RD, Plagnol V, Robson S, et al. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature. 2010;464(7289):713&#x2013;720.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2892339</ArticleId><ArticleId IdType="pubmed">20360734</ArticleId></ArticleIdList></Reference><Reference><Citation>Adarichev VA, Vermes C, Hanyecz A, Mikecz K, Bremer EG, Glant TT. Gene expression profiling in murine autoimmune arthritis during the initiation and progression of joint inflammation. Arthritis Res Ther. 2005;7(2):R196&#x2013;R207.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1065315</ArticleId><ArticleId IdType="pubmed">15743466</ArticleId></ArticleIdList></Reference><Reference><Citation>Ahlqvist E, Hultqvist M, Holmdahl R. The value of animal models in predicting genetic susceptibility to complex diseases such as rheumatoid arthritis. Arthritis Res Ther. 2009;11(3):226.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2714094</ArticleId><ArticleId IdType="pubmed">19490601</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Finnegan A, Mikecz K. Proteoglycan-induced arthritis: immune regulation, cellular mechanisms, and genetics. Crit Rev Immunol. 2003;23(3):199&#x2013;250.</Citation><ArticleIdList><ArticleId IdType="pubmed">14584879</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Mikecz K, Arzoumanian A, Poole AR. Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum. 1987;30(2):201&#x2013;212.</Citation><ArticleIdList><ArticleId IdType="pubmed">3827960</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Adarichev VA, Nesterovitch AB, Szanto S, Oswald JP, Jacobs JJ, et al. Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis. Am J Med Sci. 2004;327(4):188&#x2013;195.</Citation><ArticleIdList><ArticleId IdType="pubmed">15084914</ArticleId></ArticleIdList></Reference><Reference><Citation>Deighton CM, Walker DJ, Griffiths ID, Roberts DF. The contribution of HLA to rheumatoid arthritis. Clin Genet. 1989;36(3):178&#x2013;182.</Citation><ArticleIdList><ArticleId IdType="pubmed">2676268</ArticleId></ArticleIdList></Reference><Reference><Citation>Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987;30(11):1205&#x2013;1213.</Citation><ArticleIdList><ArticleId IdType="pubmed">2446635</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Woude D, Houwing-Duistermaat JJ, Toes RE, Huizinga TW, Thomson W, Worthington J, et al. Quantitative heritability of anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis. Arthritis Rheum. 2009;60(4):916&#x2013;923.</Citation><ArticleIdList><ArticleId IdType="pubmed">19333951</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Helm-van Mil AH, Verpoort KN, le Cessie S, Huizinga TW, de Vries RR, Toes RE. The HLA-DRB1 shared epitope alleles differ in the interaction with smoking and predisposition to antibodies to cyclic citrullinated peptide. Arthritis Rheum. 2007;56(2):425&#x2013;432.</Citation><ArticleIdList><ArticleId IdType="pubmed">17265477</ArticleId></ArticleIdList></Reference><Reference><Citation>du Montcel ST, Michou L, Petit-Teixeira E, Osorio J, Lemaire I, Lasbleiz S, et al. New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility. Arthritis Rheum. 2005;52(4):1063&#x2013;1068.</Citation><ArticleIdList><ArticleId IdType="pubmed">15818663</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Woude D, Lie BA, Lundstrom E, Balsa A, Feitsma AL, Houwing-Duistermaat JJ, et al. Protection against anti-citrullinated protein antibody-positive rheumatoid arthritis is predominantly associated with HLA-DRB1*1301: a meta-analysis of HLADRB1 associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in four European populations. Arthritis Rheum. 2010;62(5):1236&#x2013;1245.</Citation><ArticleIdList><ArticleId IdType="pubmed">20131291</ArticleId></ArticleIdList></Reference><Reference><Citation>Laki J, Lundstrom E, Snir O, Ronnelid J, Ganji I, Catrina AI, et al. Very high levels of anti-citrullinated protein antibodies are associated with HLA-DRB1*15 non-shared epitope allele in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64(7):2078&#x2013;2084.</Citation><ArticleIdList><ArticleId IdType="pubmed">22307773</ArticleId></ArticleIdList></Reference><Reference><Citation>Zsilak S, Gal J, Hodinka L, Rajczy K, Balog A, Sipka S, et al. HLA-DR genotypes in familial rheumatoid arthritis: increased frequency of protective and neutral alleles in a multicase family. J Rheumatol. 2005;32(12):2299&#x2013;2302.</Citation><ArticleIdList><ArticleId IdType="pubmed">16331753</ArticleId></ArticleIdList></Reference><Reference><Citation>Jawaheer D, Thomson W, MacGregor AJ, Carthy D, Davidson J, Dyer PA, et al. "Homozygosity" for the HLA-DR shared epitope contributes the highest risk for rheumatoid arthritis concordance in identical twins. Arthritis Rheum. 1994;37(5):681&#x2013;686.</Citation><ArticleIdList><ArticleId IdType="pubmed">7514412</ArticleId></ArticleIdList></Reference><Reference><Citation>Gyetvai A, Szekanecz Z, Soos L, Szabo Z, Fekete A, Kapitany A, et al. New classification of the shared epitope in rheumatoid arthritis: impact on the production of various anti-citrullinated protein antibodies. Rheumatology (Oxford) 2009</Citation><ArticleIdList><ArticleId IdType="pubmed">19920092</ArticleId></ArticleIdList></Reference><Reference><Citation>Huizinga TW, Amos CI, van der Helm-van Mil AH, Chen W, van Gaalen FA, Jawaheer D, et al. Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum. 2005;52(11):3433&#x2013;3438.</Citation><ArticleIdList><ArticleId IdType="pubmed">16255021</ArticleId></ArticleIdList></Reference><Reference><Citation>Bax M, van Heemst J, Huizinga TW, Toes RE. Genetics of rheumatoid arthritis: what have we learned? Immunogenetics. 2011;63(8):459&#x2013;466.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3132380</ArticleId><ArticleId IdType="pubmed">21556860</ArticleId></ArticleIdList></Reference><Reference><Citation>Farago B, Magyari L, Safrany E, Csongei V, Jaromi L, Horvatovich K, et al. Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis. Ann Rheum Dis. 2008;67(2):248&#x2013;250.</Citation><ArticleIdList><ArticleId IdType="pubmed">17606463</ArticleId></ArticleIdList></Reference><Reference><Citation>Farago B, Talian GC, Komlosi K, Nagy G, Berki T, Gyetvai A, et al. Protein tyrosine phosphatase gene C1858T allele confers risk for rheumatoid arthritis in Hungarian subjects. Rheumatol Int. 2009;29(7):793&#x2013;796.</Citation><ArticleIdList><ArticleId IdType="pubmed">19034456</ArticleId></ArticleIdList></Reference><Reference><Citation>Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet. 2010;42(6):508&#x2013;514.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4243840</ArticleId><ArticleId IdType="pubmed">20453842</ArticleId></ArticleIdList></Reference><Reference><Citation>Goeb V, Dieude P, Daveau R, Thomas-L'otellier M, Jouen F, Hau F, et al. Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid factor and anticitrullinated protein antibodies to very early rheumatoid arthritis diagnosis. Rheumatology (Oxford) 2008;47(8):1208&#x2013;1212.</Citation><ArticleIdList><ArticleId IdType="pubmed">18535030</ArticleId></ArticleIdList></Reference><Reference><Citation>Cha S, Choi CB, Han TU, Kang CP, Kang C, Bae SC. Association of anti-cyclic citrullinated peptide antibody levels with PADI4 haplotypes in early rheumatoid arthritis and with shared epitope alleles in very late rheumatoid arthritis. Arthritis Rheum. 2007;56(5):1454&#x2013;1463.</Citation><ArticleIdList><ArticleId IdType="pubmed">17469103</ArticleId></ArticleIdList></Reference><Reference><Citation>Poor G, Nagy ZB, Schmidt Z, Brozik M, Meretey K, Gergely P., Jr Genetic background of anticyclic citrullinated peptide autoantibody production in Hungarian patients with rheumatoid arthritis. Ann N Y Acad Sci. 2007;1110:23&#x2013;32.</Citation><ArticleIdList><ArticleId IdType="pubmed">17911417</ArticleId></ArticleIdList></Reference><Reference><Citation>Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003;34(4):395&#x2013;402.</Citation><ArticleIdList><ArticleId IdType="pubmed">12833157</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Linden MP, Feitsma AL, le Cessie S, Kern M, Olsson LM, Raychaudhuri S, et al. Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis. Arthritis Rheum. 2009;60(8):2242&#x2013;2247.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3121053</ArticleId><ArticleId IdType="pubmed">19644859</ArticleId></ArticleIdList></Reference><Reference><Citation>Liang YL, Wu H, Shen X, Li PQ, Yang XQ, Liang L, et al. Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis. Mol Biol Rep. 2012</Citation><ArticleIdList><ArticleId IdType="pubmed">22714917</ArticleId></ArticleIdList></Reference><Reference><Citation>Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, et al. TRAF1-C5 as a risk locus for rheumatoid arthritis&#x2014;a genomewide study. N Engl J Med. 2007;357(12):1199&#x2013;1209.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2636867</ArticleId><ArticleId IdType="pubmed">17804836</ArticleId></ArticleIdList></Reference><Reference><Citation>Lee YH, Ji JD, Song GG. Associations between FCGR3A polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. J Rheumatol. 2008;35(11):2129&#x2013;2135.</Citation><ArticleIdList><ArticleId IdType="pubmed">18843786</ArticleId></ArticleIdList></Reference><Reference><Citation>Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, et al. A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genet. 2010;42(6):515&#x2013;519.</Citation><ArticleIdList><ArticleId IdType="pubmed">20453841</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE, Tak PP. Chemokine and chemokine receptor blockade in arthritis, a prototype of immune-mediated inflammatory diseases. Neth J Med. 2011;69(9):356&#x2013;366.</Citation><ArticleIdList><ArticleId IdType="pubmed">21978977</ArticleId></ArticleIdList></Reference><Reference><Citation>Ding B, Padyukov L, Lundstrom E, Seielstad M, Plenge RM, Oksenberg JR, et al. Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region. Arthritis Rheum. 2009;60(1):30&#x2013;38.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2874319</ArticleId><ArticleId IdType="pubmed">19116921</ArticleId></ArticleIdList></Reference><Reference><Citation>Verpoort KN, Cheung K, Ioan-Facsinay A, van der Helm-van Mil AH, de Vries-Bouwstra JK, Allaart CF, et al. Fine specificity of the anti-citrullinated protein antibody response is influenced by the shared epitope alleles. Arthritis Rheum. 2007;56(12):3949&#x2013;3952.</Citation><ArticleIdList><ArticleId IdType="pubmed">18050209</ArticleId></ArticleIdList></Reference><Reference><Citation>Daha NA, Toes RE. Rheumatoid arthritis: Are ACPA-positive and ACPA-negative RA the same disease? Nat Rev Rheumatol. 2011;7(4):202&#x2013;203.</Citation><ArticleIdList><ArticleId IdType="pubmed">21455249</ArticleId></ArticleIdList></Reference><Reference><Citation>Pedersen M, Jacobsen S, Klarlund M, Pedersen BV, Wiik A, Wohlfahrt J, et al. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res Ther. 2006;8(4):R133.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1779386</ArticleId><ArticleId IdType="pubmed">16872514</ArticleId></ArticleIdList></Reference><Reference><Citation>Perricone C, Ceccarelli F, Valesini G. An overview on the genetic of rheumatoid arthritis: a never-ending story. Autoimmun Rev. 10(10):599&#x2013;608.</Citation><ArticleIdList><ArticleId IdType="pubmed">21545847</ArticleId></ArticleIdList></Reference><Reference><Citation>Ruyssen-Witrand A, Rouanet S, Combe B, Dougados M, Le Loet X, Sibilia J, et al. Fcgamma receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. 2012;71(6):875&#x2013;877.</Citation><ArticleIdList><ArticleId IdType="pubmed">22368231</ArticleId></ArticleIdList></Reference><Reference><Citation>van Ede AE, Laan RF, Blom HJ, Huizinga TW, Haagsma CJ, Giesendorf BA, et al. The C677T mutation in the methyl-enetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arthritis Rheum. 2001;44(11):2525&#x2013;2530.</Citation><ArticleIdList><ArticleId IdType="pubmed">11710708</ArticleId></ArticleIdList></Reference><Reference><Citation>Berkun Y, Levartovsky D, Rubinow A, Orbach H, Aamar S, Grenader T, et al. Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. Ann Rheum Dis. 2004;63(10):1227&#x2013;1231.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1754756</ArticleId><ArticleId IdType="pubmed">15361376</ArticleId></ArticleIdList></Reference><Reference><Citation>Dervieux T, Kremer J, Lein DO, Capps R, Barham R, Meyer G, et al. Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis. Pharmacogenetics. 2004;14(11):733&#x2013;739.</Citation><ArticleIdList><ArticleId IdType="pubmed">15564880</ArticleId></ArticleIdList></Reference><Reference><Citation>Pawlik A, Wrzesniewska J, Fiedorowicz-Fabrycy I, Gawronska-Szklarz B. The MDR1 3435 polymorphism in patients with rheumatoid arthritis. Int J Clin Pharmacol Ther. 2004;42(9):496&#x2013;503.</Citation><ArticleIdList><ArticleId IdType="pubmed">15487808</ArticleId></ArticleIdList></Reference><Reference><Citation>Tolusso B, Pietrapertosa D, Morelli A, De Santis M, Gremese E, Farina G, et al. IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein plasma levels and response to therapy. Pharmacogenomics. 2006;7(5):683&#x2013;695.</Citation><ArticleIdList><ArticleId IdType="pubmed">16886894</ArticleId></ArticleIdList></Reference><Reference><Citation>van Vollenhoven RF. Switching between anti-tumour necrosis factors: trying to get a handle on a complex issue. Ann Rheum Dis. 2007;66(7):849&#x2013;851.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1955116</ArticleId><ArticleId IdType="pubmed">17576784</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23251214</PMID><DateCompleted><Year>2013</Year><Month>08</Month><Day>12</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>21</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1740-2530</ISSN><JournalIssue CitedMedium="Internet"><Volume>2012</Volume><PubDate><Year>2012</Year></PubDate></JournalIssue><Title>Clinical &amp; developmental immunology</Title><ISOAbbreviation>Clin Dev Immunol</ISOAbbreviation></Journal><ArticleTitle>Non-MHC risk alleles in rheumatoid arthritis and in the syntenic chromosome regions of corresponding animal models.</ArticleTitle><Pagination><StartPage>284751</StartPage><MedlinePgn>284751</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">284751</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1155/2012/284751</ELocationID><Abstract><AbstractText>Rheumatoid arthritis (RA) is a polygenic autoimmune disease primarily affecting the synovial joints. Numerous animal models show similarities to RA in humans; some of them not only mimic the clinical phenotypes but also demonstrate the involvement of homologous genomic regions in RA. This paper compares corresponding non-MHC genomic regions identified in rodent and human genome-wide association studies (GWAS). To date, over 30 non-MHC RA-associated loci have been identified in humans, and over 100 arthritis-associated loci have been identified in rodent models of RA. The genomic regions associated with the disease are designated by the name(s) of the gene having the most frequent and consistent RA-associated SNPs or a function suggesting their involvement in inflammatory or autoimmune processes. Animal studies on rats and mice preferentially have used single sequence length polymorphism (SSLP) markers to identify disease-associated qualitative and quantitative trait loci (QTLs) in the genome of F2 hybrids of arthritis-susceptible and arthritis-resistant rodent strains. Mouse GWAS appear to be far ahead of rat studies, and significantly more mouse QTLs correspond to human RA risk alleles.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Faculty of Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen 4012, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kadar</LastName><ForeName>Andras</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Tryniszewska</LastName><ForeName>Beata</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Kurko</LastName><ForeName>Julia</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Rauch</LastName><ForeName>Tibor A</ForeName><Initials>TA</Initials></Author><Author ValidYN="Y"><LastName>Glant</LastName><ForeName>Tibor T</ForeName><Initials>TT</Initials></Author><Author ValidYN="Y"><LastName>Mikecz</LastName><ForeName>Katalin</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zoltan</ForeName><Initials>Z</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AR059356</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR045652</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR040310</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR040310</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR059356</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR062991</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 AR045652</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2012</Year><Month>12</Month><Day>06</Day></ArticleDate></Article><MedlineJournalInfo><Country>Egypt</Country><MedlineTA>Clin Dev Immunol</MedlineTA><NlmUniqueID>101183692</NlmUniqueID><ISSNLinking>1740-2522</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000483" MajorTopicYN="Y">Alleles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002875" MajorTopicYN="N">Chromosomes</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="Y">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016678" MajorTopicYN="N">Genome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055106" MajorTopicYN="N">Genome-Wide Association Study</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008285" MajorTopicYN="N">Major Histocompatibility Complex</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D040641" MajorTopicYN="N">Quantitative Trait Loci</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2012</Year><Month>6</Month><Day>12</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2012</Year><Month>8</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2012</Year><Month>9</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>12</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>12</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>8</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2012</Year><Month>12</Month><Day>6</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">23251214</ArticleId><ArticleId IdType="pmc">PMC3521484</ArticleId><ArticleId IdType="doi">10.1155/2012/284751</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Kurko J, Besenyei T, Laki J, et al. Genetics of rheumatoid arthritis. Clinical Reviews in Allergy &amp; Immunology. In press.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3655138</ArticleId><ArticleId IdType="pubmed">23288628</ArticleId></ArticleIdList></Reference><Reference><Citation>Berg WBVD. Lessons from animal models of arthritis over the past decade. Arthritis Research and Therapy. 2009;11(5, article 250)</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2787282</ArticleId><ArticleId IdType="pubmed">19849822</ArticleId></ArticleIdList></Reference><Reference><Citation>Ahlqvist E, Hultqvist M, Holmdahl R. The value of animal models in predicting genetic susceptibility to complex diseases such as rheumatoid arthritis. Arthritis Research and Therapy. 2009;11(3, article 226)</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2714094</ArticleId><ArticleId IdType="pubmed">19490601</ArticleId></ArticleIdList></Reference><Reference><Citation>Bevaart L, Vervoordeldonk MJ, Tak PP. Evaluation of therapeutic targets in animal models of arthritis: how does it relate to rheumatoid arthritis? Arthritis and Rheumatism. 2010;62(8):2192&#x2013;2205.</Citation><ArticleIdList><ArticleId IdType="pubmed">20506322</ArticleId></ArticleIdList></Reference><Reference><Citation>Cai C, La Cava A. Mimicking self-antigens with synthetic peptides in systemic autoimmune rheumatic diseases. Current Clinical Pharmacology. 2009;4(2):142&#x2013;147.</Citation><ArticleIdList><ArticleId IdType="pubmed">19442079</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Mikecz K, Arzoumanian A, Poole AR. Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis and Rheumatism. 1987;30(2):201&#x2013;212.</Citation><ArticleIdList><ArticleId IdType="pubmed">3827960</ArticleId></ArticleIdList></Reference><Reference><Citation>Mikecz K, Glant TT, Poole AR. Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis and Rheumatism. 1987;30(3):306&#x2013;318.</Citation><ArticleIdList><ArticleId IdType="pubmed">3566822</ArticleId></ArticleIdList></Reference><Reference><Citation>Trentham DE, Townes AS, Kang AH. Autoimmunity to type II collagen: an experimental model of arthritis. Journal of Experimental Medicine. 1977;146(3):857&#x2013;868.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2180804</ArticleId><ArticleId IdType="pubmed">894190</ArticleId></ArticleIdList></Reference><Reference><Citation>Courtenay JS, Dallman MJ, Dayan AD. Immunisation against heterologous type II collagen induces arthritis in mice. Nature. 1980;283(5748):666&#x2013;668.</Citation><ArticleIdList><ArticleId IdType="pubmed">6153460</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Finnegan A, Mikecz K. Proteoglycan-induced arthritis: immune regulation, cellular mechanisms, and genetics. Critical Reviews in Immunology. 2003;23(3):199&#x2013;250.</Citation><ArticleIdList><ArticleId IdType="pubmed">14584879</ArticleId></ArticleIdList></Reference><Reference><Citation>Popovic M, Ahlqvist E, Rockenbauer E, Bockermann R, Holmdahl R. Identification of new loci controlling collagen-induced arthritis in mouse using a partial advanced intercross and congenic strains. Scandinavian Journal of Immunology. 2008;68(4):405&#x2013;413.</Citation><ArticleIdList><ArticleId IdType="pubmed">18782270</ArticleId></ArticleIdList></Reference><Reference><Citation>Zanelli E, Breedveld FC, De Vries RRP. HLA class II association with rheumatoid arthritis: facts and interpretations. Human Immunology. 2000;61(12):1254&#x2013;1261.</Citation><ArticleIdList><ArticleId IdType="pubmed">11163080</ArticleId></ArticleIdList></Reference><Reference><Citation>Weyand CM, Goronzy JJ. Association of MHC and rheumatoid arthritis HLA polymorphisms in phenotypic variants of rheumatoid arthritis. Arthritis Research. 2000;2(3):212&#x2013;216.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC130005</ArticleId><ArticleId IdType="pubmed">11094432</ArticleId></ArticleIdList></Reference><Reference><Citation>Plenge RM. Rheumatoid arthritis genetics: 2009 update. Current Rheumatology Reports. 2009;11(5):351&#x2013;356.</Citation><ArticleIdList><ArticleId IdType="pubmed">19772830</ArticleId></ArticleIdList></Reference><Reference><Citation>Bax M, Van Heemst J, Huizinga TWJ, Toes REM. Genetics of rheumatoid arthritis: what have we learned? Immunogenetics. 2011;63(8):459&#x2013;466.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3132380</ArticleId><ArticleId IdType="pubmed">21556860</ArticleId></ArticleIdList></Reference><Reference><Citation>Perricone C, Ceccarelli F, Valesini G. An overview on the genetic of rheumatoid arthritis: a never-ending story. Autoimmunity Reviews. 2011;10(10):599&#x2013;608.</Citation><ArticleIdList><ArticleId IdType="pubmed">21545847</ArticleId></ArticleIdList></Reference><Reference><Citation>Craddock N, Hurles ME, Cardin N, et al. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature. 2010;464(7289):713&#x2013;720.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2892339</ArticleId><ArticleId IdType="pubmed">20360734</ArticleId></ArticleIdList></Reference><Reference><Citation>Cong F, Spencer S, C&#xf4;t&#xe9; JF, et al. Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation. Molecular Cell. 2000;6(6):1413&#x2013;1423.</Citation><ArticleIdList><ArticleId IdType="pubmed">11163214</ArticleId></ArticleIdList></Reference><Reference><Citation>Stahl EA, Raychaudhuri S, Remmers EF, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nature Genetics. 2010;42(6):508&#x2013;514.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC4243840</ArticleId><ArticleId IdType="pubmed">20453842</ArticleId></ArticleIdList></Reference><Reference><Citation>de Vries R. Genetics of rheumatoid arthritis: time for a change! Current Opinion in Rheumatology. 2011;23(3):227&#x2013;232.</Citation><ArticleIdList><ArticleId IdType="pubmed">21427575</ArticleId></ArticleIdList></Reference><Reference><Citation>Velaga MR, Wilson V, Jennings CE, et al. The codon 620 tryptophan allele of the Lymphoid Tyrosine Phosphatase (LYP) gene is a major determinant of Graves&#x2019; disease. Journal of Clinical Endocrinology and Metabolism. 2004;89(11):5862&#x2013;5865.</Citation><ArticleIdList><ArticleId IdType="pubmed">15531553</ArticleId></ArticleIdList></Reference><Reference><Citation>Smyth D, Cooper JD, Collins JE, et al. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes. 2004;53(11):3020&#x2013;3023.</Citation><ArticleIdList><ArticleId IdType="pubmed">15504986</ArticleId></ArticleIdList></Reference><Reference><Citation>Criswell LA, Pfeiffer KA, Lum RF, et al. Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. American Journal of Human Genetics. 2005;76(4):561&#x2013;571.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1199294</ArticleId><ArticleId IdType="pubmed">15719322</ArticleId></ArticleIdList></Reference><Reference><Citation>Hinks A, Barton A, John S, et al. Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Arthritis and Rheumatism. 2005;52(6):1694&#x2013;1699.</Citation><ArticleIdList><ArticleId IdType="pubmed">15934099</ArticleId></ArticleIdList></Reference><Reference><Citation>Viken MK, Amundsen SS, Kvien TK, et al. Association analysis of the 1858C &gt; T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases. Genes and Immunity. 2005;6(3):271&#x2013;273.</Citation><ArticleIdList><ArticleId IdType="pubmed">15759012</ArticleId></ArticleIdList></Reference><Reference><Citation>De Jager PL, Sawcer S, Waliszewska A, et al. Evaluating the role of the 620W allele of protein tyrosine phosphatase PTPN22 in Crohn&#x2019;s disease and multiple sclerosis. European Journal of Human Genetics. 2006;14(3):317&#x2013;321.</Citation><ArticleIdList><ArticleId IdType="pubmed">16391555</ArticleId></ArticleIdList></Reference><Reference><Citation>Vandiedonck C, Capdevielle C, Giraud M, et al. Association of the PTPN22&#x2217;R620W polymorphism with autoimmune myasthenia gravis. Annals of Neurology. 2006;59(2):404&#x2013;407.</Citation><ArticleIdList><ArticleId IdType="pubmed">16437561</ArticleId></ArticleIdList></Reference><Reference><Citation>Centola M, Szekanecz Z, Kiss E, et al. Gene expression profiles of systemic lupus erythematosus and rheumatoid arthritis. Expert Review of Clinical Immunology. 2007;3(5):797&#x2013;806.</Citation><ArticleIdList><ArticleId IdType="pubmed">20477029</ArticleId></ArticleIdList></Reference><Reference><Citation>Coenen MJH, Gregersen PK. Rheumatoid arthritis: a view of the current genetic landscape. Genes and Immunity. 2009;10(2):101&#x2013;111.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2730780</ArticleId><ArticleId IdType="pubmed">18987647</ArticleId></ArticleIdList></Reference><Reference><Citation>Brand DD, Kang AH, Rosloniec EF. Immunopathogenesis of collagen arthritis. Springer Seminars in Immunopathology. 2003;25(1):3&#x2013;18.</Citation><ArticleIdList><ArticleId IdType="pubmed">12904888</ArticleId></ArticleIdList></Reference><Reference><Citation>Hanyecz A, Berlo SE, Sz&#xe1;nt&#xf3; S, Broeren CPM, Mikecz K, Glant TT. Achievement of a synergistic adjuvant effect on arthritis induction by activation of innate immunity and forcing the immune response toward the Th1 phenotype. Arthritis and Rheumatism. 2004;50(5):1665&#x2013;1676.</Citation><ArticleIdList><ArticleId IdType="pubmed">15146438</ArticleId></ArticleIdList></Reference><Reference><Citation>Kouskoff V, Korganow AS, Duchatelle V, Degott C, Benoist C, Mathis D. Organ-specific disease provoked by systemic autoimmunity. Cell. 1996;87(5):811&#x2013;822.</Citation><ArticleIdList><ArticleId IdType="pubmed">8945509</ArticleId></ArticleIdList></Reference><Reference><Citation>Korganow AS, Hong J, Mangialaio S, et al. From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins. Immunity. 1999;10(4):451&#x2013;461.</Citation><ArticleIdList><ArticleId IdType="pubmed">10229188</ArticleId></ArticleIdList></Reference><Reference><Citation>Mangialaio S, Ji H, Korganow AS, et al. The arthritogenic T cell receptor and its ligand in a model of spontaneous arthritis. Arthritis and Rheumatism. 1999;42(12):2517&#x2013;2523.</Citation><ArticleIdList><ArticleId IdType="pubmed">10615996</ArticleId></ArticleIdList></Reference><Reference><Citation>Matsumoto I, Maccioni M, Lee DM, et al. How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease. Nature Immunology. 2002;3(4):360&#x2013;365.</Citation><ArticleIdList><ArticleId IdType="pubmed">11896391</ArticleId></ArticleIdList></Reference><Reference><Citation>Kassahn D, Kolb C, Solomon S, et al. Few human autoimmune sera detect GPI (multiple letters) [2] Nature Immunology. 2002;3(5):411&#x2013;413.</Citation><ArticleIdList><ArticleId IdType="pubmed">11976712</ArticleId></ArticleIdList></Reference><Reference><Citation>Kassahn D, Kolb C, Solomon S, et al. Few human autoimmune sera detect GPI (multiple letters) Nature Immunology. 2002;3(5):411&#x2013;413.</Citation><ArticleIdList><ArticleId IdType="pubmed">11976712</ArticleId></ArticleIdList></Reference><Reference><Citation>Matsumoto I, Lee DM, Goldbach-Mansky R, et al. Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders. Arthritis and Rheumatism. 2003;48(4):944&#x2013;954.</Citation><ArticleIdList><ArticleId IdType="pubmed">12687536</ArticleId></ArticleIdList></Reference><Reference><Citation>Johnsen AK, Valdar W, Golden L, et al. A genome-wide and species-wide dissection of the genetics of arthritis severity in hetrogeneous stock mice. Arthritis and Rheumatism. 2011;63(9):2630&#x2013;2640.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3371645</ArticleId><ArticleId IdType="pubmed">21560115</ArticleId></ArticleIdList></Reference><Reference><Citation>Sakaguchi N, Takahashi T, Hata H, et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 2003;426(6965):454&#x2013;460.</Citation><ArticleIdList><ArticleId IdType="pubmed">14647385</ArticleId></ArticleIdList></Reference><Reference><Citation>Horai R, Saijo S, Tanioka H, et al. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin I receptor antagonist-deficient mice. Journal of Experimental Medicine. 2000;191(2):313&#x2013;320.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2195765</ArticleId><ArticleId IdType="pubmed">10637275</ArticleId></ArticleIdList></Reference><Reference><Citation>Nakae S, Saijo S, Horai R, Sudo K, Mori S, Iwakura Y. IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(10):5986&#x2013;5990.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC156313</ArticleId><ArticleId IdType="pubmed">12721360</ArticleId></ArticleIdList></Reference><Reference><Citation>Keffer J, Probert L, Cazlaris H, et al. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO Journal. 1991;10(13):4025&#x2013;4031.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC453150</ArticleId><ArticleId IdType="pubmed">1721867</ArticleId></ArticleIdList></Reference><Reference><Citation>Solomon S, Rajasekaran N, Jeisy-Walder E, Snapper SB, Illges H. A crucial role for macrophages in the pathology of K/B &#xd7; N serum-induced arthritis. European Journal of Immunology. 2005;35(10):3064&#x2013;3073.</Citation><ArticleIdList><ArticleId IdType="pubmed">16180250</ArticleId></ArticleIdList></Reference><Reference><Citation>Stuart JM, Dixon FJ. Serum transfer of collagen-induced arthritis in mice. Journal of Experimental Medicine. 1983;158(2):378&#x2013;392.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2187334</ArticleId><ArticleId IdType="pubmed">6886622</ArticleId></ArticleIdList></Reference><Reference><Citation>Englert ME, Ferguson KM, Suarez CR. Passive transfer of collagen arthritis: heterogeneity of anti-collagen IgG. Cellular Immunology. 1986;101(2):373&#x2013;379.</Citation><ArticleIdList><ArticleId IdType="pubmed">2428515</ArticleId></ArticleIdList></Reference><Reference><Citation>Holmdahl R, Klareskog L, Rubin K. T lymphocytes in collagen II-induced arthritis in mice. Characterization of arthritogenic collagen II-specific T-cell lines and clones. Scandinavian Journal of Immunology. 1985;22(3):295&#x2013;306.</Citation><ArticleIdList><ArticleId IdType="pubmed">2413528</ArticleId></ArticleIdList></Reference><Reference><Citation>Tarjanyi O, Boldizsar F, Nemeth P, Mikecz K, Glant TT. Age-related changes in arthritis susceptibility and severity in a murine model of rheumatoid arthritis. Immunity and Ageing. 2009;6, article 8</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2704168</ArticleId><ArticleId IdType="pubmed">19519881</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Radacs M, Nagyeri G, et al. Proteoglycan-induced arthritis and recombinant human proteoglycan aggrecan G1 domain-induced arthritis in BALB/c mice resembling two subtypes of rheumatoid arthritis. Arthritis and Rheumatism. 2011;63(5):1312&#x2013;1321.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3086933</ArticleId><ArticleId IdType="pubmed">21305522</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang Y, Guerassimov A, Leroux JY, et al. Induction of arthritis in BALB/c mice by cartilage link protein: involvement of distinct regions recognized by T and B lymphocytes. American Journal of Pathology. 1998;153(4):1283&#x2013;1291.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1853050</ArticleId><ArticleId IdType="pubmed">9777960</ArticleId></ArticleIdList></Reference><Reference><Citation>Verheijden GFM, Rijnders AWM, Bos E, et al. Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis. Arthritis and Rheumatism. 1997;40(6):1115&#x2013;1125.</Citation><ArticleIdList><ArticleId IdType="pubmed">9182922</ArticleId></ArticleIdList></Reference><Reference><Citation>B&#xe1;rdos T, Zhang J, Mikecz K, David CS, Glant TT. Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age. Arthritis and Rheumatism. 2002;46(9):2465&#x2013;2475.</Citation><ArticleIdList><ArticleId IdType="pubmed">12355495</ArticleId></ArticleIdList></Reference><Reference><Citation>Berlo SE, Van Kooten PJ, Ten Brink CB, et al. Naive transgenic T cells expressing cartilage proteoglycan-specific TCR induce arthritis upon in vivo activation. Journal of Autoimmunity. 2005;25(3):172&#x2013;180.</Citation><ArticleIdList><ArticleId IdType="pubmed">16257179</ArticleId></ArticleIdList></Reference><Reference><Citation>Berlo SE, Guichelaar T, Ten Brink CB, et al. Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-transgenic mice. Arthritis and Rheumatism. 2006;54(8):2423&#x2013;2433.</Citation><ArticleIdList><ArticleId IdType="pubmed">16869010</ArticleId></ArticleIdList></Reference><Reference><Citation>Boldizsar F, Kis-Toth K, Tarjanyi O, et al. Impaired activation-induced cell death promotes spontaneous arthritis in antigen (cartilage proteoglycan)-specific T cell receptor-transgenic mice. Arthritis and Rheumatism. 2010;62(10):2984&#x2013;2994.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2952044</ArticleId><ArticleId IdType="pubmed">20564001</ArticleId></ArticleIdList></Reference><Reference><Citation>Jensen JR, Peters LC, Borrego A, et al. Involvement of antibody production quantitative trait loci in the susceptibility to pristane-induced arthritis in the mouse. Genes and Immunity. 2006;7(1):44&#x2013;50.</Citation><ArticleIdList><ArticleId IdType="pubmed">16435023</ArticleId></ArticleIdList></Reference><Reference><Citation>Yu X, Bauer K, Koczan D, Thiesen HJ, Ibrahim SM. Combining global genome and transcriptome approaches to identify the candidate genes of small-effect quantitative trait loci in collagen-induced arthritis. Arthritis Research and Therapy. 2007;9, article R3</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1860061</ArticleId><ArticleId IdType="pubmed">17244351</ArticleId></ArticleIdList></Reference><Reference><Citation>Yu X, Teng H, Marques A, Ashgari F, Ibrahim SM. High resolution mapping of Cia3: a common arthritis quantitative trait loci in different species. Journal of Immunology. 2009;182(5):3016&#x2013;3023.</Citation><ArticleIdList><ArticleId IdType="pubmed">19234197</ArticleId></ArticleIdList></Reference><Reference><Citation>Poole AR. Cartilage in health and disease. In: McCarty DJ, Koopman WJ, editors. Arthritis and Allied Conditions. A Textbook of Rheumatology. Philadelphia, Pa, USA: Lea &amp; Febiger; 1993. pp. 279&#x2013;333.</Citation></Reference><Reference><Citation>Czipri M, Otto JM, Cs-Szab&#xf3; G, et al. Genetic rescue of chondrodysplasia and the perinatal lethal effect of cartilage link protein deficiency. Journal of Biological Chemistry. 2003;278(40):39214&#x2013;39223.</Citation><ArticleIdList><ArticleId IdType="pubmed">12732630</ArticleId></ArticleIdList></Reference><Reference><Citation>Singer II, Kawka DW, Bayne EK, et al. VDIPEN, a metalloproteinase-generated neoepitope, is induced and immunolocalized in articular cartilage during inflammatory arthritis. Journal of Clinical Investigation. 1995;95(5):2178&#x2013;2186.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC295822</ArticleId><ArticleId IdType="pubmed">7537757</ArticleId></ArticleIdList></Reference><Reference><Citation>Bizzaro N. Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis. Clinical Chemistry and Laboratory Medicine. 2007;45(2):150&#x2013;157.</Citation><ArticleIdList><ArticleId IdType="pubmed">17311500</ArticleId></ArticleIdList></Reference><Reference><Citation>Simon M, Girbal E, Sebbag M, et al. The cytokeratin filament-aggregating protein filaggrin is the target of the so-called &#x2019;antikeratin antibodies,&#x2019; autoantibodies specific for rheumatoid arthritis. Journal of Clinical Investigation. 1993;92(3):1387&#x2013;1393.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC288281</ArticleId><ArticleId IdType="pubmed">7690781</ArticleId></ArticleIdList></Reference><Reference><Citation>Girbal-Neuhauser E, Durieux JJ, Arnaud M, et al. The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. Journal of Immunology. 1999;162(1):585&#x2013;594.</Citation><ArticleIdList><ArticleId IdType="pubmed">9886436</ArticleId></ArticleIdList></Reference><Reference><Citation>Poole AR, Glant TT, Mikecz K. Autoimmunity to cartilage collagen and proteoglycan and the development of chronic inflammatory arthritis. In: Glaurer AM, editor. The Control of Tissue Damage. Amsterdam, The Netherlands: Elsevier Publishers (Biomedical Division); 1988. pp. 55&#x2013;65.</Citation></Reference><Reference><Citation>Glant TT, Mikecz K, Thonar EJMA, Kuettner KE. Immune responses to cartilage proteoglycans in inflammatory animal models and human diseases. In: Woessner JF, Howell DS, editors. Cartilage Degradation: Basic and Clinical Aspects. New York, NY, USA: Marcel Dekker; 1992. pp. 435&#x2013;473.</Citation></Reference><Reference><Citation>Glant TT, Fulop C, Mikecz K, Buzas E, Molnar G, Erhardt P. Proteoglycan-specific autoreactive antibodies and T-lymphocytes in experimental arthritis and human rheumatoid joint diseases. Biochemical Society Transactions. 1990;18(5):796&#x2013;799.</Citation><ArticleIdList><ArticleId IdType="pubmed">2083679</ArticleId></ArticleIdList></Reference><Reference><Citation>Herman JH, Wiltse DW, Dennis MV. Immunopathologic significance of cartilage antigenic components in rheumatoid arthritis. Arthritis and Rheumatism. 1973;16(3):287&#x2013;297.</Citation><ArticleIdList><ArticleId IdType="pubmed">4122517</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant T, Csongor J, Szucs T. Immunopathologic role of proteoglycan antigens in rheumatoid joint disease. Scandinavian Journal of Immunology. 1980;11(3):247&#x2013;252.</Citation><ArticleIdList><ArticleId IdType="pubmed">9537052</ArticleId></ArticleIdList></Reference><Reference><Citation>Golds EE, Stephen IBM, Esdaile JM. Lymphocyte transformation to connective tissue antigens in adult and juvenile rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus, and a nonarthritic control population. Cellular Immunology. 1983;82(1):196&#x2013;209.</Citation><ArticleIdList><ArticleId IdType="pubmed">6640674</ArticleId></ArticleIdList></Reference><Reference><Citation>Karopoulos C, Rowley MJ, Ilic MZ, Handley CJ. Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases. Arthritis and Rheumatism. 1996;39(12):1990&#x2013;1997.</Citation><ArticleIdList><ArticleId IdType="pubmed">8961903</ArticleId></ArticleIdList></Reference><Reference><Citation>Boots AMH, Verheijden GFM, Sch&#xf6;ningh R, et al. Selection of self-reactive peptides within human aggrecan by use of a HLA-DRB1*0401 peptide binding motif. Journal of Autoimmunity. 1997;10(6):569&#x2013;578.</Citation><ArticleIdList><ArticleId IdType="pubmed">9451596</ArticleId></ArticleIdList></Reference><Reference><Citation>Guerassimov A, Zhang Y, Banerjee S, et al. Autoimmunity to cartilage link protein in patients with rheumatoid arthritis and ankylosing spondylitis. Journal of Rheumatology. 1998;25(8):1480&#x2013;1484.</Citation><ArticleIdList><ArticleId IdType="pubmed">9712087</ArticleId></ArticleIdList></Reference><Reference><Citation>Guerassimov A, Zhang YP, Banerjee S, et al. Cellular immunity to the G1 domain of cartilage proteoglycan aggrecan is enhanced in patients with rheumatoid arthritis but only after removal of keratan sulfate. Arthritis and Rheumatism. 1998;41(6):1019&#x2013;1025.</Citation><ArticleIdList><ArticleId IdType="pubmed">9627011</ArticleId></ArticleIdList></Reference><Reference><Citation>Li NL, Zhang DQ, Zhou KY, et al. Isolation and characteristics of autoreactive T cells specific to aggrecan G1 domain from rheumatoid arthritis patients. Cell Research. 2000;10(1):39&#x2013;49.</Citation><ArticleIdList><ArticleId IdType="pubmed">10765982</ArticleId></ArticleIdList></Reference><Reference><Citation>Zou J, Zhang Y, Thiel A, et al. Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis. Rheumatology. 2003;42(7):846&#x2013;855.</Citation><ArticleIdList><ArticleId IdType="pubmed">12730543</ArticleId></ArticleIdList></Reference><Reference><Citation>De Jong H, Berlo SE, Hombrink P, et al. Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis. Annals of the Rheumatic Diseases. 2010;69(1):255&#x2013;262.</Citation><ArticleIdList><ArticleId IdType="pubmed">19213744</ArticleId></ArticleIdList></Reference><Reference><Citation>Von Delwig A, Locke J, Robinson JH, Ng WF. Response of Th17 cells to a citrullinated arthritogenic aggrecan peptide in patients with rheumatoid arthritis. Arthritis and Rheumatism. 2010;62(1):143&#x2013;149.</Citation><ArticleIdList><ArticleId IdType="pubmed">20039419</ArticleId></ArticleIdList></Reference><Reference><Citation>Law SC, Street S, Yu CH, et al. T cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles. Arthritis Research and Therapy. 2012;14(3):p. R118.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3446499</ArticleId><ArticleId IdType="pubmed">22594821</ArticleId></ArticleIdList></Reference><Reference><Citation>Buz&#xe1;s EI, Hanyecz A, Murad Y, et al. Differential recognition of altered peptide ligands distinguishes two functionally discordant (arthritogenic and nonarthritogenic) autoreactive T cell hybridoma clones. Journal of Immunology. 2003;171(6):3025&#x2013;3033.</Citation><ArticleIdList><ArticleId IdType="pubmed">12960328</ArticleId></ArticleIdList></Reference><Reference><Citation>Buz&#xe1;s EI, V&#xe9;gv&#xe1;ri A, Murad YM, Finnegan A, Mikecz K, Glant TT. T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis. Cellular Immunology. 2005;235(2):98&#x2013;108.</Citation><ArticleIdList><ArticleId IdType="pubmed">16185673</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Adarichev VA, Nesterovitch AB, et al. Disease-associated qualitative and quantitative trait loci in proteoglycan-induced arthritis and collagen-induced arthritis. American Journal of the Medical Sciences. 2004;327(4):188&#x2013;195.</Citation><ArticleIdList><ArticleId IdType="pubmed">15084914</ArticleId></ArticleIdList></Reference><Reference><Citation>Otto JM, Cs-Szab&#xf3; G, Gallagher J, et al. Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis. Arthritis and Rheumatism. 1999;42(12):2524&#x2013;2531.</Citation><ArticleIdList><ArticleId IdType="pubmed">10615997</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Adarichev VA, Boldizsar F, et al. Disease-promoting and -protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis. Gene Immunity. 2012;13(4):336&#x2013;345.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3524972</ArticleId><ArticleId IdType="pubmed">22402741</ArticleId></ArticleIdList></Reference><Reference><Citation>Adarichev VA, B&#xe1;rdos T, Christodoulou S, Phillips MT, Mikecz K, Glant TT. Major histocompatibility complex controls susceptibility and dominant inheritance, but not the severity of the disease in mouse models of rheumatoid arthritis. Immunogenetics. 2002;54(3):184&#x2013;192.</Citation><ArticleIdList><ArticleId IdType="pubmed">12073147</ArticleId></ArticleIdList></Reference><Reference><Citation>Adarichev VA, Valdez JC, B&#xe1;rdos T, Finnegan A, Mikecz K, Glant TT. Combined autoimmune models of arthritis reveal shared and independent qualitative (binary) and quantitative trait loci. Journal of Immunology. 2003;170(5):2283&#x2013;2292.</Citation><ArticleIdList><ArticleId IdType="pubmed">12594249</ArticleId></ArticleIdList></Reference><Reference><Citation>Adarichev VA, Vegvari A, Szabo Z, Kis-Toth K, Mikecz K, Glant TT. Congenic strains displaying similar clinical phenotype of arthritis represent different immunologic models of inflammation. Genes and Immunity. 2008;9(7):591&#x2013;601.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3951374</ArticleId><ArticleId IdType="pubmed">18650834</ArticleId></ArticleIdList></Reference><Reference><Citation>Plenge RM, Seielstad M, Padyukov L, et al. TRAF1-C5 as a risk locus for rheumatoid arthritis - A genomewide study. The New England Journal of Medicine. 2007;357(12):1199&#x2013;1209.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2636867</ArticleId><ArticleId IdType="pubmed">17804836</ArticleId></ArticleIdList></Reference><Reference><Citation>Etzel CJ, Chen WV, Shepard N, et al. Genome-wide meta-analysis for rheumatoid arthritis. Human Genetics. 2006;119(6):634&#x2013;641.</Citation><ArticleIdList><ArticleId IdType="pubmed">16612613</ArticleId></ArticleIdList></Reference><Reference><Citation>Barton A, Thomson W, Ke X, et al. Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility. Human Molecular Genetics. 2008;17(15):2274&#x2013;2279.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2465799</ArticleId><ArticleId IdType="pubmed">18434327</ArticleId></ArticleIdList></Reference><Reference><Citation>Eleftherohorinou H, Wright V, Hoggart C, et al. Pathway analysis of GWAS provides new insights into genetic susceptibility to 3 inflammatory diseases. PloS One. 2009;4(11, article e8068)</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2778995</ArticleId><ArticleId IdType="pubmed">19956648</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Sz&#xe1;nt&#xf3; S, Vegvari A, et al. Two loci on chromosome 15 control experimentally induced arthritis through the differential regulation of IL-6 and lymphocyte proliferation. Journal of Immunology. 2008;181(2):1307&#x2013;1314.</Citation><ArticleIdList><ArticleId IdType="pubmed">18606685</ArticleId></ArticleIdList></Reference><Reference><Citation>Ahlqvist E, Bockermann R, Holmdahl R. Fragmentation of two quantitative trait loci controlling collagen-induced arthritis reveals a new set of interacting subloci. Journal of Immunology. 2007;178(5):3084&#x2013;3090.</Citation><ArticleIdList><ArticleId IdType="pubmed">17312155</ArticleId></ArticleIdList></Reference><Reference><Citation>Liljander M, S&#xe4;llstr&#xf6;m MA, Anderson S, et al. Identification of collagen-induced arthritis loci in aged multiparous female mice. Arthritis Research and Therapy. 2006;8(2, article R45)</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1526604</ArticleId><ArticleId IdType="pubmed">16507151</ArticleId></ArticleIdList></Reference><Reference><Citation>Bauer K, Yu X, Wernhoff P, Koczan D, Thiesen HJ, Ibrahim SM. Identification of new quantitative trait loci in mice with collagen-induced arthritis. Arthritis and Rheumatism. 2004;50(11):3721&#x2013;3728.</Citation><ArticleIdList><ArticleId IdType="pubmed">15529344</ArticleId></ArticleIdList></Reference><Reference><Citation>Yu X, Bauer K, Wernhoff P, et al. Fine mapping of collagen-induced arthritis quantitative trait loci in an advanced intercross line. Journal of Immunology. 2006;177(10):7042&#x2013;7049.</Citation><ArticleIdList><ArticleId IdType="pubmed">17082620</ArticleId></ArticleIdList></Reference><Reference><Citation>Johannesson M, Olsson LM, Lindqvist AKB, et al. Gene expression profiling of arthritis using a QTL chip reveals a complex gene regulation of the Cia5 region in mice. Genes and Immunity. 2005;6(7):575&#x2013;583.</Citation><ArticleIdList><ArticleId IdType="pubmed">16015370</ArticleId></ArticleIdList></Reference><Reference><Citation>Lindvall T, Karlsson J, Holmdahl R, et al. Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes. Arthritis Research and Therapy. 2009;11(1, article R10)</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2688241</ArticleId><ArticleId IdType="pubmed">20527086</ArticleId></ArticleIdList></Reference><Reference><Citation>Ibrahim SM, Koczan D, Thiesen HJ. Gene-expression profile of collagen-induced arthritis. Journal of Autoimmunity. 2002;18(2):159&#x2013;167.</Citation><ArticleIdList><ArticleId IdType="pubmed">11908948</ArticleId></ArticleIdList></Reference><Reference><Citation>Gulko PS, Kawahito Y, Remmers EF, et al. Identification of a new non-major histocompatibility complex genetic locus on chromosome 2 that controls disease severity in collagen-induced arthritis in rats. Arthritis and Rheumatism. 1998;41(12):2122&#x2013;2131.</Citation><ArticleIdList><ArticleId IdType="pubmed">9870869</ArticleId></ArticleIdList></Reference><Reference><Citation>Kawahito Y, Remmers EF, Wilder RL, et al. A genetic linkage map of rat chromosome 20 derived from five F2 crosses. Immunogenetics. 1998;48(5):335&#x2013;338.</Citation><ArticleIdList><ArticleId IdType="pubmed">9745010</ArticleId></ArticleIdList></Reference><Reference><Citation>Shepard JS, Remmers EF, Chen S, et al. A genetic linkage map of rat Chromosome 15 derived from five F2 crosses. Mammalian Genome. 1999;10(2):186&#x2013;188.</Citation><ArticleIdList><ArticleId IdType="pubmed">9922401</ArticleId></ArticleIdList></Reference><Reference><Citation>Joe B, Remmers EF, Dobbins DE, et al. Genetic dissection of collagen-induced arthritis in chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences. Immunogenetics. 2000;51(11):930&#x2013;944.</Citation><ArticleIdList><ArticleId IdType="pubmed">11003387</ArticleId></ArticleIdList></Reference><Reference><Citation>Wester L, Olofsson P, Ibrahim SM, Holmdahl R. Chronicity of pristane-induced arthritis in rats is controlled by genes on chromosome 14. Journal of Autoimmunity. 2003;21(4):305&#x2013;313.</Citation><ArticleIdList><ArticleId IdType="pubmed">14624754</ArticleId></ArticleIdList></Reference><Reference><Citation>Wester L, Koczan D, Holmberg J, et al. Differential gene expression in pristane-induced arthritis susceptible DA versus resistant E3 rats. Arthritis Research &amp; Therapy. 2003;5(6):R361&#x2013;R372.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC333422</ArticleId><ArticleId IdType="pubmed">14680511</ArticleId></ArticleIdList></Reference><Reference><Citation>Adarichev VA, Nesterovitch AB, B&#xe1;rdos T, et al. Sex effect on clinical and immunologic quantitative trait loci in a murine model of rheumatoid arthritis. Arthritis and Rheumatism. 2003;48(6):1708&#x2013;1720.</Citation><ArticleIdList><ArticleId IdType="pubmed">12794840</ArticleId></ArticleIdList></Reference><Reference><Citation>Otto JM, Chandrasekeran R, Vermes C, et al. A genome scan using a novel genetic cross identifies new susceptibility loci and traits in a mouse model of rheumatoid arthritis. Journal of Immunology. 2000;165(9):5278&#x2013;5286.</Citation><ArticleIdList><ArticleId IdType="pubmed">11046062</ArticleId></ArticleIdList></Reference><Reference><Citation>Johannesson M, Karlsson J, Wernhoff P, et al. Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice. Genes and Immunity. 2005;6(3):175&#x2013;185.</Citation><ArticleIdList><ArticleId IdType="pubmed">15716976</ArticleId></ArticleIdList></Reference><Reference><Citation>Firneisz G, Zehavi I, Vermes C, Hanyecz A, Frieman JA, Glant TT. Identification and quantification of disease-related gene clusters. Bioinformatics. 2003;19(14):1781&#x2013;1786.</Citation><ArticleIdList><ArticleId IdType="pubmed">14512349</ArticleId></ArticleIdList></Reference><Reference><Citation>Yang HT, Jirholt J, Svensson L, et al. Identification of genes controlling collagen-induced arthritis in mice: striking homology with susceptibility loci previously identified in the rat. Journal of Immunology. 1999;163(5):2916&#x2013;2921.</Citation><ArticleIdList><ArticleId IdType="pubmed">10453039</ArticleId></ArticleIdList></Reference><Reference><Citation>Van Houten N, Blake SF. Direct measurement of anergy of antigen-specific T cells following oral tolerance induction. Journal of Immunology. 1996;157(4):1337&#x2013;1341.</Citation><ArticleIdList><ArticleId IdType="pubmed">8759712</ArticleId></ArticleIdList></Reference><Reference><Citation>Studelska DR, Mandik-Nayak L, Zhou X, et al. High affinity glycosaminoglycan and autoantigen interaction explains joint specificity in a mouse model of rheumatoid arthritis. Journal of Biological Chemistry. 2009;284(4):2354&#x2013;2362.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2629098</ArticleId><ArticleId IdType="pubmed">18948258</ArticleId></ArticleIdList></Reference><Reference><Citation>Hughes LB, Reynolds RJ, Brown EE, et al. Most common single-nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans. Arthritis and Rheumatism. 2010;62(12):3547&#x2013;3553.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3030622</ArticleId><ArticleId IdType="pubmed">21120996</ArticleId></ArticleIdList></Reference><Reference><Citation>Cui J, Saevarsdottir S, Thomson B, et al. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor &#x3b1; therapy. Arthritis and Rheumatism. 2010;62(7):1849&#x2013;1861.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3652476</ArticleId><ArticleId IdType="pubmed">20309874</ArticleId></ArticleIdList></Reference><Reference><Citation>Thompson SD, Sudman M, Ramos PS, et al. The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1. Arthritis and Rheumatism. 2010;62(11):3265&#x2013;3276.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2970764</ArticleId><ArticleId IdType="pubmed">20722033</ArticleId></ArticleIdList></Reference><Reference><Citation>Morgan AW, Robinson JI, Conaghan PG, et al. Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort. Arthritis Research and Therapy. 2010;12(2, article R57)</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2888207</ArticleId><ArticleId IdType="pubmed">20353580</ArticleId></ArticleIdList></Reference><Reference><Citation>Freudenberg J, Lee HS, Han BG, et al. Genome-Wide Association Study of Rheumatoid Arthritis in Koreans: population-specific loci as well as overlap with European Susceptibility Loci. Arthritis and Rheumatism. 2011;63(4):884&#x2013;893.</Citation><ArticleIdList><ArticleId IdType="pubmed">21452313</ArticleId></ArticleIdList></Reference><Reference><Citation>Plenge RM, Cotsapas C, Davies L, et al. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nature Genetics. 2007;39(12):1477&#x2013;1482.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2652744</ArticleId><ArticleId IdType="pubmed">17982456</ArticleId></ArticleIdList></Reference><Reference><Citation>Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annual Review of Immunology. 1996;14:397&#x2013;440.</Citation><ArticleIdList><ArticleId IdType="pubmed">8717520</ArticleId></ArticleIdList></Reference><Reference><Citation>Menard L, Saadoun D, Isnardi I, et al. The PTPN22 allele encoding an R620W variant interferes with the removal of developing autoreactive B cells in humans. The Journal of Clinical Investigation. 2011;121(9):3635&#x2013;3644.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3163953</ArticleId><ArticleId IdType="pubmed">21804190</ArticleId></ArticleIdList></Reference><Reference><Citation>Jirholt J, Cook A, Emahazion T, et al. Genetic linkage analysis of collagen-induced arthritis in the mouse. European Journal of Immunology. 1998;28(10):3321&#x2013;3328.</Citation><ArticleIdList><ArticleId IdType="pubmed">9808201</ArticleId></ArticleIdList></Reference><Reference><Citation>Sundvall M, Jirholt J, Yang HT, et al. Identification of murine loci associated with susceptibility to chronic experimental autoimmune encephalomyelitis. Nature Genetics. 1995;10(3):313&#x2013;317.</Citation><ArticleIdList><ArticleId IdType="pubmed">7545492</ArticleId></ArticleIdList></Reference><Reference><Citation>Karlsson J, Johannesson M, Lindvall T, et al. Genetic interactions in Eae2 control collagen-induced arthritis and the CD4+/CD8+ T cell ratio. Journal of Immunology. 2005;174(1):533&#x2013;541.</Citation><ArticleIdList><ArticleId IdType="pubmed">15611280</ArticleId></ArticleIdList></Reference><Reference><Citation>Meng HC, Griffiths MM, Remmers EF, et al. Identification of two novel female-specific non-major histocompatibility complex loci regulating collagen-induced arthritis severity and chronicity, and evidence of epistasis. Arthritis and Rheumatism. 2004;50(8):2695&#x2013;2705.</Citation><ArticleIdList><ArticleId IdType="pubmed">15334486</ArticleId></ArticleIdList></Reference><Reference><Citation>Brenner M, Meng HC, Yarlett NC, et al. The non-major histocompatibility complex quantitative trait locus Cia10 contains a major arthritis gene and regulates disease severity, pannus formation, and joint damage. Arthritis and Rheumatism. 2005;52(1):322&#x2013;332.</Citation><ArticleIdList><ArticleId IdType="pubmed">15641042</ArticleId></ArticleIdList></Reference><Reference><Citation>Xu W, Lan H, Hu P, et al. Evidence of linkage to chromosome 1 for early age of onset of rheumatoid arthritis and HLA marker DRB1 genotype in NARAC data. BMC Proceedings. 2007;1(supplement 1):p. S78.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2367509</ArticleId><ArticleId IdType="pubmed">18466580</ArticleId></ArticleIdList></Reference><Reference><Citation>Liu C, Batliwalla F, Li W, et al. Genome-wide association scan identifies candidate polymorphisms associated with differential response to anti-TNF treatment in rheumatoid arthritis. Molecular Medicine. 2008;14(9-10):575&#x2013;581.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2276142</ArticleId><ArticleId IdType="pubmed">18615156</ArticleId></ArticleIdList></Reference><Reference><Citation>Gharaee-Kermani M, Denholm EM, Phan SH. Costimulation of fibroblast collagen and transforming growth factor &#x3b2;1 gene expression by monocyte chemoattractant protein-1 via specific receptors. Journal of Biological Chemistry. 1996;271(30):17779&#x2013;17784.</Citation><ArticleIdList><ArticleId IdType="pubmed">8663511</ArticleId></ArticleIdList></Reference><Reference><Citation>van der Helm-van Mil AHM, Huizinga TWJ. Advances in the genetics of rheumatoid arthritis point to subclassification into distinct disease subsets. Arthritis Research and Therapy. 2008;10(2, article 205)</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2453775</ArticleId><ArticleId IdType="pubmed">18394179</ArticleId></ArticleIdList></Reference><Reference><Citation>Bowes J, Barton A. Recent advances in the genetics of RA susceptibility. Rheumatology. 2008;47(4):399&#x2013;402.</Citation><ArticleIdList><ArticleId IdType="pubmed">18263596</ArticleId></ArticleIdList></Reference><Reference><Citation>Choi SJ, Rho YH, Ji JD, Song GG, Lee YH. Genome scan meta-analysis of rheumatoid arthritis. Rheumatology. 2006;45(2):166&#x2013;170.</Citation><ArticleIdList><ArticleId IdType="pubmed">16278286</ArticleId></ArticleIdList></Reference><Reference><Citation>Morgan AW, Barrett JH, Griffiths B, et al. Analysis of Fcgamma receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B. Arthritis Research &amp; Therapy. 2006;8(1):p. R5.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1526569</ArticleId><ArticleId IdType="pubmed">16356189</ArticleId></ArticleIdList></Reference><Reference><Citation>Kochi Y, Yamada R, Suzuki A, et al. A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nature Genetics. 2005;37(5):478&#x2013;485.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1362949</ArticleId><ArticleId IdType="pubmed">15838509</ArticleId></ArticleIdList></Reference><Reference><Citation>Licatalosi DD, Mele A, Fak JJ, et al. HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature. 2008;456(7221):464&#x2013;469.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2597294</ArticleId><ArticleId IdType="pubmed">18978773</ArticleId></ArticleIdList></Reference><Reference><Citation>Chi SW, Zang JB, Mele A, Darnell RB. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature. 2009;460(7254):479&#x2013;486.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2733940</ArticleId><ArticleId IdType="pubmed">19536157</ArticleId></ArticleIdList></Reference><Reference><Citation>Malterer G, D&#xf6;lken L, Haas J. The miRNA-targetome of KSHV and EBV in human B-cells. RNA Biology. 2011;8(1):30&#x2013;34.</Citation><ArticleIdList><ArticleId IdType="pubmed">21301209</ArticleId></ArticleIdList></Reference><Reference><Citation>Wen J, Parker BJ, Jacobsen A, Krogh A. MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action. RNA. 2011;17(5):820&#x2013;834.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3078732</ArticleId><ArticleId IdType="pubmed">21389147</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang C, Darnell RB. Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data. Nature Biotechnology. 2011;29(7):607&#x2013;614.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3400429</ArticleId><ArticleId IdType="pubmed">21633356</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22492217</PMID><DateCompleted><Year>2013</Year><Month>01</Month><Day>16</Day></DateCompleted><DateRevised><Year>2022</Year><Month>03</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1529-0131</ISSN><JournalIssue CitedMedium="Internet"><Volume>64</Volume><Issue>10</Issue><PubDate><Year>2012</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Arthritis and rheumatism</Title><ISOAbbreviation>Arthritis Rheum</ISOAbbreviation></Journal><ArticleTitle>Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis.</ArticleTitle><Pagination><StartPage>3179</StartPage><EndPage>3188</EndPage><MedlinePgn>3179-88</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/art.34494</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To determine whether myeloid cells (such as granulocytes) present in the synovial fluid (SF) of arthritic joints have an impact on adaptive immunity. Specifically, we investigated the effects of SF cells harvested from the joints of mice with proteoglycan-induced arthritis (PGIA), on dendritic cell (DC) maturation and antigen-specific T cell proliferation.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We monitored DC maturation (MHCII and CD86 expression) by flow cytometry upon coculture of DCs with SF cells or spleen myeloid cells from mice with PGIA. The effects of these myeloid cells on T cell proliferation were studied using T cells purified from PG-specific T cell receptor (TCR)-transgenic (Tg) mice. Phenotype analysis of myeloid cells was performed by immunostaining, reverse transcription-polymerase chain reaction, Western blotting, and biochemical assays.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Inflammatory SF cells significantly suppressed the maturation of DCs upon coculture. PG-TCR-Tg mouse T cells cultured with antigen-loaded DCs showed dramatic decreases in proliferation in the presence of SF cells. Spleen myeloid cells from arthritic mice did not have suppressive effects. SF cells were unable to suppress CD3/CD28-stimulated proliferation of the same T cells, suggesting a DC-dependent mechanism. SF cells exhibited all of the characteristics of myeloid-derived suppressor cells (MDSCs) and exerted suppression primarily through the production of nitric oxide and reactive oxygen species by granulocyte-like cells.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">SF in the joints of mice with PGIA contains a population of granulocytic MDSCs that potently suppress DC maturation and T cell proliferation. These MDSCs have the potential to limit the expansion of autoreactive T cells, thus breaking the vicious cycle of autoimmunity and inflammation.</AbstractText><CopyrightInformation>Copyright &#xa9; 2012 by the American College of Rheumatology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Egelston</LastName><ForeName>Colt</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Rush University Medical Center, Chicago, Illinois 60612, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kurk&#xf3;</LastName><ForeName>J&#xfa;lia</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Tryniszewska</LastName><ForeName>Beata</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Rauch</LastName><ForeName>Tibor A</ForeName><Initials>TA</Initials></Author><Author ValidYN="Y"><LastName>Glant</LastName><ForeName>Tibor T</ForeName><Initials>TT</Initials></Author><Author ValidYN="Y"><LastName>Mikecz</LastName><ForeName>Katalin</ForeName><Initials>K</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AR051163-05</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR-051163</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 AR062332-01</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 AR062332</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR-062332</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR051163</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Arthritis Rheum</MedlineTA><NlmUniqueID>0370605</NlmUniqueID><ISSNLinking>0004-3591</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001169" MajorTopicYN="N">Arthritis, Experimental</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D049109" MajorTopicYN="Y">Cell Proliferation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D022423" MajorTopicYN="N">Myeloid Cells</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013582" MajorTopicYN="N">Synovial Fluid</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013601" MajorTopicYN="N">T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><CoiStatement>None of the authors has financial conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2012</Year><Month>4</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2012</Year><Month>4</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2013</Year><Month>1</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2013</Year><Month>10</Month><Day>1</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">22492217</ArticleId><ArticleId IdType="mid">NIHMS368398</ArticleId><ArticleId IdType="pmc">PMC3402579</ArticleId><ArticleId IdType="doi">10.1002/art.34494</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Bjelle A, Norberg B, Sjogren G. The cytology of joint exudates in rheumatoid arthritis. Morphology and preparation techniques. Scand J Rheumatol. 1982;11:124&#x2013;128.</Citation><ArticleIdList><ArticleId IdType="pubmed">7089502</ArticleId></ArticleIdList></Reference><Reference><Citation>Yamamoto T, Nishiura H, Nishida H. Molecular mechanisms to form leukocyte infiltration patterns distinct between synovial tissue and fluid of rheumatoid arthritis. Semin Thromb Hemost. 1996;22:507&#x2013;511.</Citation><ArticleIdList><ArticleId IdType="pubmed">9122716</ArticleId></ArticleIdList></Reference><Reference><Citation>Wipke BT, Allen PM. Essential role of neutrophils in the initiation and progression of a murine model of rheumatoid arthritis. J Immunol. 2001;167:1601&#x2013;1608.</Citation><ArticleIdList><ArticleId IdType="pubmed">11466382</ArticleId></ArticleIdList></Reference><Reference><Citation>Griffiths RJ, Pettipher ER, Koch K, Farrell CA, Breslow R, Conklyn MJ, et al. Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis. Proc Natl Acad Sci U S A. 1995;92:517&#x2013;521.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC42772</ArticleId><ArticleId IdType="pubmed">7831322</ArticleId></ArticleIdList></Reference><Reference><Citation>Wipke BT, Wang Z, Nagengast W, Reichert DE, Allen PM. Staging the initiation of autoantibody-induced arthritis: a critical role for immune complexes. J Immunol. 2004;172:7694&#x2013;7702.</Citation><ArticleIdList><ArticleId IdType="pubmed">15187152</ArticleId></ArticleIdList></Reference><Reference><Citation>Sarraj B, Ludanyi K, Glant TT, Finnegan A, Mikecz K. Expression of CD44 and L-selectin in the innate immune system is required for severe joint inflammation in the proteoglycan-induced murine model of rheumatoid arthritis. J Immunol. 2006;177:1932&#x2013;1940.</Citation><ArticleIdList><ArticleId IdType="pubmed">16849507</ArticleId></ArticleIdList></Reference><Reference><Citation>Angyal A, Egelston C, Kobezda T, Olasz K, Laszlo A, Glant TT, et al. Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody production, but does not involve significant influx of T cells into the joints. Arthritis Res Ther. 2010;12:R44.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2888192</ArticleId><ArticleId IdType="pubmed">20298547</ArticleId></ArticleIdList></Reference><Reference><Citation>Wright HL, Moots RJ, Bucknall RC, Edwards SW. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford) 2010;49:1618&#x2013;1631.</Citation><ArticleIdList><ArticleId IdType="pubmed">20338884</ArticleId></ArticleIdList></Reference><Reference><Citation>Santiago-Schwarz F, Anand P, Liu S, Carsons SE. Dendritic cells (DCs) in rheumatoid arthritis (RA): progenitor cells and soluble factors contained in RA synovial fluid yield a subset of myeloid DCs that preferentially activate Th1 inflammatory-type responses. J Immunol. 2001;167:1758&#x2013;1768.</Citation><ArticleIdList><ArticleId IdType="pubmed">11466401</ArticleId></ArticleIdList></Reference><Reference><Citation>Jongbloed SL, Lebre MC, Fraser AR, Gracie JA, Sturrock RD, Tak PP, et al. Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis. Arthritis Res Ther. 2006;8:R15.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1526567</ArticleId><ArticleId IdType="pubmed">16507115</ArticleId></ArticleIdList></Reference><Reference><Citation>Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245&#x2013;252.</Citation><ArticleIdList><ArticleId IdType="pubmed">9521319</ArticleId></ArticleIdList></Reference><Reference><Citation>van Gisbergen KP, Sanchez-Hernandez M, Geijtenbeek TB, van Kooyk Y. Neutrophils mediate immune modulation of dendritic cells through glycosylation-dependent interactions between Mac-1 and DC-SIGN. J Exp Med. 2005;201:1281&#x2013;1292.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2213143</ArticleId><ArticleId IdType="pubmed">15837813</ArticleId></ArticleIdList></Reference><Reference><Citation>Bennouna S, Bliss SK, Curiel TJ, Denkers EY. Cross-talk in the innate immune system: neutrophils instruct recruitment and activation of dendritic cells during microbial infection. J Immunol. 2003;171:6052&#x2013;6058.</Citation><ArticleIdList><ArticleId IdType="pubmed">14634118</ArticleId></ArticleIdList></Reference><Reference><Citation>Bennouna S, Denkers EY. Microbial antigen triggers rapid mobilization of TNF-alpha to the surface of mouse neutrophils transforming them into inducers of high-level dendritic cell TNF-alpha production. J Immunol. 2005;174:4845&#x2013;4851.</Citation><ArticleIdList><ArticleId IdType="pubmed">15814711</ArticleId></ArticleIdList></Reference><Reference><Citation>Youn JI, Gabrilovich DI. The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur J Immunol. 2010;40:2969&#x2013;2975.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3277452</ArticleId><ArticleId IdType="pubmed">21061430</ArticleId></ArticleIdList></Reference><Reference><Citation>Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9:162&#x2013;174.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2828349</ArticleId><ArticleId IdType="pubmed">19197294</ArticleId></ArticleIdList></Reference><Reference><Citation>Youn JI, Nagaraj S, Collazo M, Gabrilovich DI. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol. 2008;181:5791&#x2013;5802.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2575748</ArticleId><ArticleId IdType="pubmed">18832739</ArticleId></ArticleIdList></Reference><Reference><Citation>Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol. 2005;5:641&#x2013;654.</Citation><ArticleIdList><ArticleId IdType="pubmed">16056256</ArticleId></ArticleIdList></Reference><Reference><Citation>Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L, et al. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med. 2007;13:828&#x2013;835.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2135607</ArticleId><ArticleId IdType="pubmed">17603493</ArticleId></ArticleIdList></Reference><Reference><Citation>Harari O, Liao JK. Inhibition of MHC II gene transcription by nitric oxide and antioxidants. Curr Pharm Des. 2004;10:893&#x2013;898.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2633593</ArticleId><ArticleId IdType="pubmed">15032692</ArticleId></ArticleIdList></Reference><Reference><Citation>Berlo SE, Guichelaar T, ten Brink CB, Van Kooten PJ, Hauet-Broere F, Ludanyi K, et al. Increased arthritis susceptibility in cartilage proteoglycan-specific T cell receptor-transgenic mice. Arthritis Rheum. 2006;54:2423&#x2013;2433.</Citation><ArticleIdList><ArticleId IdType="pubmed">16869010</ArticleId></ArticleIdList></Reference><Reference><Citation>Faust N, Varas F, Kelly LM, Heck S, Graf T. Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. Blood. 2000;96:719&#x2013;726.</Citation><ArticleIdList><ArticleId IdType="pubmed">10887140</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Mikecz K, Arzoumanian A, Poole AR. Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum. 1987;30:201&#x2013;212.</Citation><ArticleIdList><ArticleId IdType="pubmed">3827960</ArticleId></ArticleIdList></Reference><Reference><Citation>Mikecz K, Glant TT, Poole AR. Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis Rheum. 1987;30:306&#x2013;318.</Citation><ArticleIdList><ArticleId IdType="pubmed">3566822</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Finnegan A, Mikecz K. Proteoglycan-induced arthritis: immune regulation, cellular mechanisms and genetics. Crit Rev Immunol. 2003;23:199&#x2013;250.</Citation><ArticleIdList><ArticleId IdType="pubmed">14584879</ArticleId></ArticleIdList></Reference><Reference><Citation>Hanyecz A, Berlo SE, Szanto S, Broeren CPM, Mikecz K, Glant TT. Achievement of a synergistic adjuvant effect on arthritis induction by activation of innate immunity and forcing the immune response toward the Th1 phenotype. Arthritis Rheum. 2004;50:1665&#x2013;1676.</Citation><ArticleIdList><ArticleId IdType="pubmed">15146438</ArticleId></ArticleIdList></Reference><Reference><Citation>Glant TT, Radacs M, Nagyeri G, Olasz K, Laszlo A, Boldizsar F, et al. Proteoglycan-induced arthritis and recombinant human proteoglycan aggrecan G1 domain-induced arthritis in BALB/c mice resembling two types of rheumatoid arthritis. Arthritis Rheum. 2011;63:1312&#x2013;1321.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3086933</ArticleId><ArticleId IdType="pubmed">21305522</ArticleId></ArticleIdList></Reference><Reference><Citation>Lutz MB, Kukutsch N, Ogilvie AL, Rossner S, Koch F, Romani N, et al. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods. 1999;223:77&#x2013;92.</Citation><ArticleIdList><ArticleId IdType="pubmed">10037236</ArticleId></ArticleIdList></Reference><Reference><Citation>Germain RN, Bhattacharya A, Dorf ME, Springer TA. A single monoclonal anti-Ia antibody inhibits antigen-specific T cell proliferation controlled by distinct Ir genes mapping in different H-2 I subregions. J Immunol. 1982;128:1409&#x2013;1413.</Citation><ArticleIdList><ArticleId IdType="pubmed">6173436</ArticleId></ArticleIdList></Reference><Reference><Citation>Ferraro C, Quemeneur L, Fournel S, Prigent AF, Revillard JP, Bonnefoy-Berard N. The topoisomerase inhibitors camptothecin and etoposide induce a CD95-independent apoptosis of activated peripheral lymphocytes. Cell Death Differ. 2000;7:197&#x2013;206.</Citation><ArticleIdList><ArticleId IdType="pubmed">10713734</ArticleId></ArticleIdList></Reference><Reference><Citation>Rudolf K, Cervinka M, Rudolf E. Dual inhibition of topoisomerases enhances apoptosis in melanoma cells. Neoplasma. 2010;57:316&#x2013;324.</Citation><ArticleIdList><ArticleId IdType="pubmed">20429622</ArticleId></ArticleIdList></Reference><Reference><Citation>Corraliza IM, Campo ML, Soler G, Modolell M. Determination of arginase activity in macrophages: a micromethod. J Immunol Methods. 1994;174:231&#x2013;235.</Citation><ArticleIdList><ArticleId IdType="pubmed">8083527</ArticleId></ArticleIdList></Reference><Reference><Citation>Kusmartsev S, Gabrilovich DI. Inhibition of myeloid cell differentiation in cancer: the role of reactive oxygen species. J Leukoc Biol. 2003;74:186&#x2013;196.</Citation><ArticleIdList><ArticleId IdType="pubmed">12885935</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhu B, Bando Y, Xiao S, Yang K, Anderson AC, Kuchroo VK, et al. CD11b+Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis. J Immunol. 2007;179:5228&#x2013;5237.</Citation><ArticleIdList><ArticleId IdType="pubmed">17911608</ArticleId></ArticleIdList></Reference><Reference><Citation>Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, et al. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res. 2005;65:3044&#x2013;3048.</Citation><ArticleIdList><ArticleId IdType="pubmed">15833831</ArticleId></ArticleIdList></Reference><Reference><Citation>Sallusto F, Lanzavecchia A. The instructive role of dendritic cells on T-cell responses. Arthritis Res. 2002;4 (Suppl 3):S127&#x2013;S132.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3240143</ArticleId><ArticleId IdType="pubmed">12110131</ArticleId></ArticleIdList></Reference><Reference><Citation>Henrickson SE, Mempel TR, Mazo IB, Liu B, Artyomov MN, Zheng H, et al. T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation. Nat Immunol. 2008;9:282&#x2013;291.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2698867</ArticleId><ArticleId IdType="pubmed">18204450</ArticleId></ArticleIdList></Reference><Reference><Citation>Makarenkova VP, Bansal V, Matta BM, Perez LA, Ochoa JB. CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic stress. J Immunol. 2006;176:2085&#x2013;2094.</Citation><ArticleIdList><ArticleId IdType="pubmed">16455964</ArticleId></ArticleIdList></Reference><Reference><Citation>Schmielau J, Finn OJ. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients. Cancer Res. 2001;61:4756&#x2013;4760.</Citation><ArticleIdList><ArticleId IdType="pubmed">11406548</ArticleId></ArticleIdList></Reference><Reference><Citation>Lim MB, Kuiper JW, Katchky A, Goldberg H, Glogauer M. Rac2 is required for the formation of neutrophil extracellular traps. J Leukoc Biol. 2011;90:771&#x2013;776.</Citation><ArticleIdList><ArticleId IdType="pubmed">21712395</ArticleId></ArticleIdList></Reference><Reference><Citation>Kumar S, Jyoti A, Keshari RS, Singh M, Barthwal MK, Dikshit M. Functional and molecular characterization of NOS isoforms in rat neutrophil precursor cells. Cytometry A. 2010;77:467&#x2013;477.</Citation><ArticleIdList><ArticleId IdType="pubmed">20104578</ArticleId></ArticleIdList></Reference><Reference><Citation>Bansal S, Siddarth M, Chawla D, Banerjee BD, Madhu SV, Tripathi AK. Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro. Mol Cell Biochem. 2012;361:289&#x2013;296.</Citation><ArticleIdList><ArticleId IdType="pubmed">22048812</ArticleId></ArticleIdList></Reference><Reference><Citation>Xu W, Firestein GS, Taetle R, Kaushansky K, Zvaifler NJ. Cytokines in chronic inflammatory arthritis. II. Granulocyte- macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest. 1989;83:876&#x2013;882.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC303761</ArticleId><ArticleId IdType="pubmed">2646320</ArticleId></ArticleIdList></Reference><Reference><Citation>Dolcetti L, Peranzoni E, Ugel S, Marigo I, Fernandez GA, Mesa C, et al. Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur J Immunol. 2010;40:22&#x2013;35.</Citation><ArticleIdList><ArticleId IdType="pubmed">19941314</ArticleId></ArticleIdList></Reference><Reference><Citation>Condamine T, Gabrilovich DI. Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function. Trends Immunol. 2011;32:19&#x2013;25.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3053028</ArticleId><ArticleId IdType="pubmed">21067974</ArticleId></ArticleIdList></Reference><Reference><Citation>Belz GT, Heath WR, Carbone FR. The role of dendritic cell subsets in selection between tolerance and immunity. Immunol Cell Biol. 2002;80:463&#x2013;468.</Citation><ArticleIdList><ArticleId IdType="pubmed">12225382</ArticleId></ArticleIdList></Reference><Reference><Citation>Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol. 2003;21:685&#x2013;711.</Citation><ArticleIdList><ArticleId IdType="pubmed">12615891</ArticleId></ArticleIdList></Reference><Reference><Citation>Yang CW, Strong BS, Miller MJ, Unanue ER. Neutrophils influence the level of antigen presentation during the immune response to protein antigens in adjuvants. J Immunol. 2010;185:2927&#x2013;2934.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3509756</ArticleId><ArticleId IdType="pubmed">20679530</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21733730</PMID><DateCompleted><Year>2012</Year><Month>07</Month><Day>02</Day></DateCompleted><DateRevised><Year>2020</Year><Month>02</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1778-7254</ISSN><JournalIssue CitedMedium="Internet"><Volume>78</Volume><Issue>6</Issue><PubDate><Year>2011</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Joint bone spine</Title><ISOAbbreviation>Joint Bone Spine</ISOAbbreviation></Journal><ArticleTitle>Associations of HLA-shared epitope, anti-citrullinated peptide antibodies and lifestyle-related factors in Hungarian patients with rheumatoid arthritis: data from the first Central-Eastern European cohort.</ArticleTitle><Pagination><StartPage>652</StartPage><EndPage>653</EndPage><MedlinePgn>652-3</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jbspin.2011.05.018</ELocationID><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Gyetvai</LastName><ForeName>Agnes</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Szab&#xf3;</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Fekete</LastName><ForeName>Andrea</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Kapit&#xe1;ny</LastName><ForeName>Anik&#xf3;</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Szodoray</LastName><ForeName>P&#xe9;ter</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Laki</LastName><ForeName>Judit</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>So&#xf3;s</LastName><ForeName>Lilla</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Sipka</LastName><ForeName>S&#xe1;ndor</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Szegedi</LastName><ForeName>Gyula</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Lakos</LastName><ForeName>Gabriella</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016422">Letter</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2011</Year><Month>07</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Joint Bone Spine</MedlineTA><NlmUniqueID>100938016</NlmUniqueID><ISSNLinking>1297-319X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000888">Antibodies, Anti-Idiotypic</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000939">Epitopes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D059811">HLA-DRB1 Chains</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010456">Peptides, Cyclic</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C487763">cyclic citrullinated peptide</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000483" MajorTopicYN="N">Alleles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000888" MajorTopicYN="N">Antibodies, Anti-Idiotypic</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000208" MajorTopicYN="N">ethnology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015331" MajorTopicYN="N">Cohort Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000939" MajorTopicYN="N">Epitopes</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005061" MajorTopicYN="N" Type="Geographic">Europe, Eastern</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020022" MajorTopicYN="N">Genetic Predisposition to Disease</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059811" MajorTopicYN="N">HLA-DRB1 Chains</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006306" MajorTopicYN="N">Health Surveys</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006814" MajorTopicYN="N" Type="Geographic">Hungary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008019" MajorTopicYN="Y">Life Style</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010456" MajorTopicYN="N">Peptides, Cyclic</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012189" MajorTopicYN="N">Retrospective Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011795" MajorTopicYN="N">Surveys and Questionnaires</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2010</Year><Month>12</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2011</Year><Month>5</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2011</Year><Month>7</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2011</Year><Month>7</Month><Day>8</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2012</Year><Month>7</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21733730</ArticleId><ArticleId IdType="doi">10.1016/j.jbspin.2011.05.018</ArticleId><ArticleId IdType="pii">S1297-319X(11)00140-0</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20305562</PMID><DateCompleted><Year>2010</Year><Month>06</Month><Day>15</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>20</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1531-6963</ISSN><JournalIssue CitedMedium="Internet"><Volume>22</Volume><Issue>3</Issue><PubDate><Year>2010</Year><Month>May</Month></PubDate></JournalIssue><Title>Current opinion in rheumatology</Title><ISOAbbreviation>Curr Opin Rheumatol</ISOAbbreviation></Journal><ArticleTitle>Angiogenesis and vasculogenesis in rheumatoid arthritis.</ArticleTitle><Pagination><StartPage>299</StartPage><EndPage>306</EndPage><MedlinePgn>299-306</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1097/BOR.0b013e328337c95a</ELocationID><Abstract><AbstractText Label="PURPOSE OF REVIEW" NlmCategory="OBJECTIVE">Angiogenesis is the formation of new capillaries from pre-existing vessels, whereas vasculogenesis is de-novo capillary formation from endothelial precursor cells (EPCs). Current understanding of the role of angiogenesis and vasculogenesis in rheumatoid arthritis (RA) and possibilities of therapeutic intervention should be summarized.</AbstractText><AbstractText Label="RECENT FINDINGS" NlmCategory="RESULTS">There have been many recent studies on the role of the hypoxia and hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF)-angiopoietin axis in angiogenesis associated with RA. The role of additional growth factors, chemokines, cytokines, matrix components and adhesion molecules has been further characterized. Macrophage migration inhibitory factor (MIF) may link inflammation, angiogenesis and atherosclerosis. Junctional adhesion molecules (JAMs) and focal adhesion kinases (FAKs) have recently been implicated in inflammatory angiogenesis. Novel information regarding the role of serum amyloid A (SAA) and sphingosine kinase has become available. Most of these angiogenic factors have recently been targeted using various techniques and arthritis models. Whereas angiogenesis is abundant in RA, there is defective EPC function and vasculogenesis leading to atherosclerosis and vascular disease in arthritis. Treatment with EPCs already under investigation in vascular diseases may also be attempted in RA.</AbstractText><AbstractText Label="SUMMARY" NlmCategory="CONCLUSIONS">Targeting angiogenesis and restoration of vasculogenesis may be beneficial for the therapy and outcome of RA.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Institute of Medicine, University of Debrecen Medical and Health Sciences Center, Hungary. szekanecz.zoltan@med.unideb.hu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Szentp&#xe9;tery</LastName><ForeName>Agnes</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Koch</LastName><ForeName>Alisa E</ForeName><Initials>AE</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AR048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR-048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Curr Opin Rheumatol</MedlineTA><NlmUniqueID>9000851</NlmUniqueID><ISSNLinking>1040-8711</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020533">Angiogenesis Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D042501">Angiogenic Proteins</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D020533" MajorTopicYN="N">Angiogenesis Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D042501" MajorTopicYN="N">Angiogenic Proteins</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="N">antagonists &amp; inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001168" MajorTopicYN="N">Arthritis</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001808" MajorTopicYN="N">Blood Vessels</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D042783" MajorTopicYN="N">Endothelial Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009389" MajorTopicYN="N">Neovascularization, Pathologic</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014652" MajorTopicYN="N">Vascular Diseases</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading></MeshHeadingList><NumberOfReferences>112</NumberOfReferences></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>3</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>3</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>6</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20305562</ArticleId><ArticleId IdType="doi">10.1097/BOR.0b013e328337c95a</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20022538</PMID><DateCompleted><Year>2010</Year><Month>05</Month><Day>04</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1778-7254</ISSN><JournalIssue CitedMedium="Internet"><Volume>77</Volume><Issue>1</Issue><PubDate><Year>2010</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Joint bone spine</Title><ISOAbbreviation>Joint Bone Spine</ISOAbbreviation></Journal><ArticleTitle>New insights in synovial angiogenesis.</ArticleTitle><Pagination><StartPage>13</StartPage><EndPage>19</EndPage><MedlinePgn>13-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jbspin.2009.05.011</ELocationID><Abstract><AbstractText>Angiogenesis is the formation of new capillaries from pre-existing vessels. A number of soluble and cell-bound factors may stimulate neovascularization. The perpetuation of angiogenesis involving numerous soluble and cell surface-bound mediators has been associated with rheumatoid arthritis (RA). These angiogenic mediators, among others, include growth factors, primarily vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as pro-inflammatory cytokines, various chemokines, cell adhesion molecules, proteases and others. Among the several potential angiogenesis inhibitors, targeting of VEGF, HIF-1, angiopoietin and the alpha(V)beta(3) integrin, as well as some endogenous or synthetic compounds including angiostatin, endostatin, paclitaxel, fumagillin analogues, 2-methoxyestradiol and thalidomide seems to be promising for the management of synovial inflammation and angiogenesis. A complete review of antiangiogenic drugs used in animal models of arthritis or human RA is available in a table.</AbstractText><CopyrightInformation>Copyright 2009 Soci&#xe9;t&#xe9; fran&#xe7;aise de rhumatologie. Published by Elsevier SAS. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Institute of Medicine, University of Debrecen Medical and Health Sciences Center, 98, Nagyerdei street, Debrecen, H-4032, Hungary. szekanecz.zoltan@med.unideb.hu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Paragh</LastName><ForeName>Gy&#xf6;rgy</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Koch</LastName><ForeName>Alisa E</ForeName><Initials>AE</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AR048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR048267-05</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR-048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>12</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Joint Bone Spine</MedlineTA><NlmUniqueID>100938016</NlmUniqueID><ISSNLinking>1297-319X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020533">Angiogenesis Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C467484">VEGFA protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D042461">Vascular Endothelial Growth Factor A</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D020533" MajorTopicYN="N">Angiogenesis Inhibitors</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009389" MajorTopicYN="N">Neovascularization, Pathologic</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013583" MajorTopicYN="N">Synovial Membrane</DescriptorName><QualifierName UI="Q000098" MajorTopicYN="Y">blood supply</QualifierName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D042461" MajorTopicYN="N">Vascular Endothelial Growth Factor A</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><CoiStatement><b>Conflicts of interest</b>. The authors have no conflicts of interest to declare.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2008</Year><Month>11</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2009</Year><Month>5</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>12</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>12</Month><Day>22</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>5</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2010</Year><Month>7</Month><Day>27</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20022538</ArticleId><ArticleId IdType="mid">NIHMS222100</ArticleId><ArticleId IdType="pmc">PMC2910514</ArticleId><ArticleId IdType="doi">10.1016/j.jbspin.2009.05.011</ArticleId><ArticleId IdType="pii">S1297-319X(09)00202-4</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Szekanecz Z, Koch AE. Vascular involvement in rheumatic diseases: &#x2018;vascular rheumatology&#x2019;. Arthritis Res Ther. 2008;10:224.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2592799</ArticleId><ArticleId IdType="pubmed">18947376</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Mechanism of disease: angiogenesis in inflammatory diseases. Nat Clin Pract Rheumatol. 2007;3:635&#x2013;643.</Citation><ArticleIdList><ArticleId IdType="pubmed">17968334</ArticleId></ArticleIdList></Reference><Reference><Citation>Lainer-Carr D, Brahn E. Angiogenesis inhibition as a therapeutic approach for inflammatory synovitis. Nat Clin Pract Rheumatol. 2007;3:434&#x2013;442.</Citation><ArticleIdList><ArticleId IdType="pubmed">17664950</ArticleId></ArticleIdList></Reference><Reference><Citation>Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;235:442&#x2013;447.</Citation><ArticleIdList><ArticleId IdType="pubmed">2432664</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Chemokines and angiogenesis. Curr Opin Rheumatol. 2001;13:202&#x2013;208.</Citation><ArticleIdList><ArticleId IdType="pubmed">11333349</ArticleId></ArticleIdList></Reference><Reference><Citation>Veale DJ, Fearon U. Inhibition of angiogenic pathways in rheumatoid arthritis: potential for therapeutic targeting. Best Pract Res Clin Rheumatol. 2006;20:941&#x2013;947.</Citation><ArticleIdList><ArticleId IdType="pubmed">16980216</ArticleId></ArticleIdList></Reference><Reference><Citation>Agarwal SK, Brenner MB. Role of adhesion molecules in synovial inflammation. Curr Opin Rheumatol. 2006;18:268&#x2013;276.</Citation><ArticleIdList><ArticleId IdType="pubmed">16582691</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Macrophages and their products in rheumatoid arthritis. Curr Opin Rheumatol. 2007;19:289&#x2013;295.</Citation><ArticleIdList><ArticleId IdType="pubmed">17414958</ArticleId></ArticleIdList></Reference><Reference><Citation>Koch AE, Harlow LA, Haines GK, et al. Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol. 1994;152:4149&#x2013;4156.</Citation><ArticleIdList><ArticleId IdType="pubmed">7511670</ArticleId></ArticleIdList></Reference><Reference><Citation>Kiselyov A, Balakin KV, Tkachenko SE. VEGF/VEGFR signaling as a target for inhibiting angiogenesis. Expert Opin Investig Drugs. 2007;16:83&#x2013;107.</Citation><ArticleIdList><ArticleId IdType="pubmed">17155856</ArticleId></ArticleIdList></Reference><Reference><Citation>Taylor PC, Sivakumar B. Hypoxia and angiogenesis in rheumatoid arthritis. Curr Opin Rheumatol. 2005;17:293&#x2013;298.</Citation><ArticleIdList><ArticleId IdType="pubmed">15838239</ArticleId></ArticleIdList></Reference><Reference><Citation>Giatromanolaki A, Sivridis E, Maltezos E, et al. Upregulated hypoxia inducible factor-1&#x3b1; and -2&#x3b1; pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2003;5:R193&#x2013;R198.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC165055</ArticleId><ArticleId IdType="pubmed">12823854</ArticleId></ArticleIdList></Reference><Reference><Citation>Arany Z, Foo SY, Ma Y, et al. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature. 2008;451:1008&#x2013;1012.</Citation><ArticleIdList><ArticleId IdType="pubmed">18288196</ArticleId></ArticleIdList></Reference><Reference><Citation>Honorati MC, Neri S, Cattini L, et al. Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts. Osteoarthritis Cartilage. 2006;14:345&#x2013;352.</Citation><ArticleIdList><ArticleId IdType="pubmed">16311048</ArticleId></ArticleIdList></Reference><Reference><Citation>Strieter RM, Polverini PJ, Kunkel SL, et al. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995;270:27348&#x2013;27357.</Citation><ArticleIdList><ArticleId IdType="pubmed">7592998</ArticleId></ArticleIdList></Reference><Reference><Citation>Pablos JL, Santiago B, Galindo M, et al. Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. J Immunol. 2003;170:2147&#x2013;2152.</Citation><ArticleIdList><ArticleId IdType="pubmed">12574387</ArticleId></ArticleIdList></Reference><Reference><Citation>Salcedo R, Ponce ML, Young HA, et al. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood. 2000;96:34&#x2013;40.</Citation><ArticleIdList><ArticleId IdType="pubmed">10891427</ArticleId></ArticleIdList></Reference><Reference><Citation>Nanki T, Hayashida K, El-Gabalawy HS, et al. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T-cell accumulation in rheumatoid arthritis synovium. J Immunol. 2000;165:6590&#x2013;6598.</Citation><ArticleIdList><ArticleId IdType="pubmed">11086103</ArticleId></ArticleIdList></Reference><Reference><Citation>Madri JA, Williams KS. Capillary endothelial cell cultures: phenotypic modulation by matrix components. J Cell Biol. 1983;97:153&#x2013;165.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2112496</ArticleId><ArticleId IdType="pubmed">6190818</ArticleId></ArticleIdList></Reference><Reference><Citation>Imhof BA, Aurrand-Lions M. Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol. 2004;4:432&#x2013;444.</Citation><ArticleIdList><ArticleId IdType="pubmed">15173832</ArticleId></ArticleIdList></Reference><Reference><Citation>Koch AE, Halloran MM, Haskell CJ, et al. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature. 1995;376:517&#x2013;519.</Citation><ArticleIdList><ArticleId IdType="pubmed">7543654</ArticleId></ArticleIdList></Reference><Reference><Citation>Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994;264:569&#x2013;571.</Citation><ArticleIdList><ArticleId IdType="pubmed">7512751</ArticleId></ArticleIdList></Reference><Reference><Citation>Naik TU, Naik MU, Naik UP. Junctional adhesion molecules in angiogenesis. Front Biosci. 2008;13:258&#x2013;262.</Citation><ArticleIdList><ArticleId IdType="pubmed">17981544</ArticleId></ArticleIdList></Reference><Reference><Citation>Jacq L, Garnier S, Dieud&#xe9; P, et al. The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study. Arthritis Res Ther. 2007;9:R63.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2206364</ArticleId><ArticleId IdType="pubmed">17615072</ArticleId></ArticleIdList></Reference><Reference><Citation>Shahrara S, Castro-Rueda HP, Haines GK, et al. Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues. Arthritis Res Ther. 2007;9:R112.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2212559</ArticleId><ArticleId IdType="pubmed">17963503</ArticleId></ArticleIdList></Reference><Reference><Citation>Kneilling M, H&#xfc;ltner L, Pichler BJ, et al. Targeted mast cell silencing protects against joint destruction and angiogenesis in experimental arthritis in mice. Arthritis Rheum. 2007;56:1806&#x2013;1816.</Citation><ArticleIdList><ArticleId IdType="pubmed">17530709</ArticleId></ArticleIdList></Reference><Reference><Citation>Brennan F, Beech J. Update on cytokines in rheumatoid arthritis. Curr Opin Rheumatol. 2007;19:296&#x2013;301.</Citation><ArticleIdList><ArticleId IdType="pubmed">17414959</ArticleId></ArticleIdList></Reference><Reference><Citation>Markham T, Mullan R, Golden-Mason L, et al. Resolution of endothelial activation and down-regulation of Tie2 receptor in psoriatic skin after infliximab therapy. J Am Acad Dermatol. 2006;54:1003&#x2013;1012.</Citation><ArticleIdList><ArticleId IdType="pubmed">16713454</ArticleId></ArticleIdList></Reference><Reference><Citation>Nakahara H, Song J, Sugimoto M, et al. Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthritis Rheum. 2003;48:1521&#x2013;1529.</Citation><ArticleIdList><ArticleId IdType="pubmed">12794819</ArticleId></ArticleIdList></Reference><Reference><Citation>Amin MA, Mansfield PJ, Pakozdi A, et al. Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways. Arthritis Rheum. 2007;56:1787&#x2013;1797.</Citation><ArticleIdList><ArticleId IdType="pubmed">17530707</ArticleId></ArticleIdList></Reference><Reference><Citation>Fearon U, Mullan R, Markham T, et al. Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures. Arthritis Rheum. 2006;54:3152&#x2013;3162.</Citation><ArticleIdList><ArticleId IdType="pubmed">17009243</ArticleId></ArticleIdList></Reference><Reference><Citation>Amin MA, Volpert OV, Woods JM, et al. Migration inhibitory factor mediates angiogenesis via mitogen-activated protein kinase and phosphatidylinositol kinase. Circ Res. 2003;93:321&#x2013;329.</Citation><ArticleIdList><ArticleId IdType="pubmed">12881477</ArticleId></ArticleIdList></Reference><Reference><Citation>Morand EF, Leech M, Bernhagen J. MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis. Nat Rev Drug Discov. 2006;5:399&#x2013;410.</Citation><ArticleIdList><ArticleId IdType="pubmed">16628200</ArticleId></ArticleIdList></Reference><Reference><Citation>Koch AE, Distler O. Vasculopathy and disordered angiogenesis in selected rheumatic diseases: rheumatoid arthritis and systemic sclerosis. Arthritis Res Ther. 2007;9 Suppl. 2:S3.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2072889</ArticleId><ArticleId IdType="pubmed">17767741</ArticleId></ArticleIdList></Reference><Reference><Citation>Mullan RH, Bresnihan B, Golden-Mason L, et al. Acute-phase serum amyloid A stimulation of angiogenesis, leukocyte recruitment and matrix degradation in rheumatoid arthritis through an NF-&#x3ba;B-dependent signal transduction pathway. Arthritis Rheum. 2006;54:105&#x2013;114.</Citation><ArticleIdList><ArticleId IdType="pubmed">16385502</ArticleId></ArticleIdList></Reference><Reference><Citation>Hong KH, Cho ML, Min SY, et al. Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid synovial fibroblasts. Clin Exp Immunol. 2007;147:573&#x2013;579.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1810499</ArticleId><ArticleId IdType="pubmed">17302909</ArticleId></ArticleIdList></Reference><Reference><Citation>Boulday G, Haskova Z, Reinders ME, et al. Vascular endothelial growth factor-induced signaling pathways in endothelial cells that mediate overexpression of the chemokine IFN-gamma-inducible protein of 10 kDa in vitro and in vivo. J Immunol. 2006;176:3098&#x2013;3107.</Citation><ArticleIdList><ArticleId IdType="pubmed">16493069</ArticleId></ArticleIdList></Reference><Reference><Citation>Vicari AP, Ait-Yahia S, Chemin K, et al. Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and immunological mechanisms. J Immunol. 2000;165:1992&#x2013;2000.</Citation><ArticleIdList><ArticleId IdType="pubmed">10925282</ArticleId></ArticleIdList></Reference><Reference><Citation>Yin G, Liu W, An P, et al. Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis. Mol Ther. 2002;5:547&#x2013;554.</Citation><ArticleIdList><ArticleId IdType="pubmed">11991745</ArticleId></ArticleIdList></Reference><Reference><Citation>Sumariwalla PF, Cao Y, Wu HL, et al. The angiogenesis inhibitor protease-activated kringles 1&#x2013;5 reduces the severity of murine collagen-induced arthritis. Arthritis Res Ther. 2003;5:R32&#x2013;R39.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC154428</ArticleId><ArticleId IdType="pubmed">12716451</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang CR, Chen SY, Shiau AL, et al. Upregulation of kallistatin expression in rheumatoid joints. J Rheumatol. 2007;34:2171&#x2013;2176.</Citation><ArticleIdList><ArticleId IdType="pubmed">17937475</ArticleId></ArticleIdList></Reference><Reference><Citation>Mundel TM, Kalluri R. Type IV collagen-derived angiogenesis inhibitors. Microvasc Res. 2007;74:85&#x2013;89.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3998721</ArticleId><ArticleId IdType="pubmed">17602710</ArticleId></ArticleIdList></Reference><Reference><Citation>Park YW, Kang YM, Butterfield J, et al. Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in rheumatoid arthritis. Am J Pathol. 2004;165:2087&#x2013;2098.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1618704</ArticleId><ArticleId IdType="pubmed">15579451</ArticleId></ArticleIdList></Reference><Reference><Citation>Haas CS, Amin MA, Allen BB, et al. Inhibition of angiogenesis by interleukin-4 gene therapy in rat adjuvant-induced arthritis. Arthritis Rheum. 2006;54:2402&#x2013;2414.</Citation><ArticleIdList><ArticleId IdType="pubmed">16869003</ArticleId></ArticleIdList></Reference><Reference><Citation>Haas CS, Amin MA, Ruth JH, et al. In vivo inhibition of angiogenesis by interleukin-13 gene therapy in a rat model of rheumatoid arthritis. Arthritis Rheum. 2007;56:2535&#x2013;2548.</Citation><ArticleIdList><ArticleId IdType="pubmed">17665443</ArticleId></ArticleIdList></Reference><Reference><Citation>Mabjeesh NJ, Escuin D, LaVallee TM, et al. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell. 2003;3:363&#x2013;375.</Citation><ArticleIdList><ArticleId IdType="pubmed">12726862</ArticleId></ArticleIdList></Reference><Reference><Citation>Issekutz AC, Sapru K. Modulation of adjuvant arthritis in the rat by 2-methoxyestradiol: an effect independent of an anti-angiogenic action. Int Immunopharmacol. 2008;8:708&#x2013;716.</Citation><ArticleIdList><ArticleId IdType="pubmed">18387513</ArticleId></ArticleIdList></Reference><Reference><Citation>Manley PW, Martiny-Baron G, Schlaeppi JM, et al. Therapies directed at vascular endothelial growth factor. Expert Opin Investig Drugs. 2002;11:1715&#x2013;1736.</Citation><ArticleIdList><ArticleId IdType="pubmed">12457433</ArticleId></ArticleIdList></Reference><Reference><Citation>Grosios K, Wood J, Esser R, et al. Angiogenesis inhibition by the novel VEGF tyrosine kinase inhibitor. PTK787/ZK222584, causes significant anti-arthritic effects in models of rheumatoid arthritis. Inflamm Res. 2004;53:133&#x2013;142.</Citation><ArticleIdList><ArticleId IdType="pubmed">15060719</ArticleId></ArticleIdList></Reference><Reference><Citation>Guttmann-Raviv N, Shraga-Heled N, Varshavsky A, et al. Semaphorin-3A and semaphorin-3F work together to repel endothelial cells and to inhibit their survival by induction of apoptosis. J Biol Chem. 2007;282:26294&#x2013;26305.</Citation><ArticleIdList><ArticleId IdType="pubmed">17569671</ArticleId></ArticleIdList></Reference><Reference><Citation>Yeo EJ, Chun YS, Cho YS, et al. YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst. 2003;95:516&#x2013;525.</Citation><ArticleIdList><ArticleId IdType="pubmed">12671019</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen Y, Donnelly E, Kobayashi H, et al. Gene therapy targeting the Tie2 function ameliorates collagen-induced arthritis and protects against bone destruction. Arthritis Rheum. 2005;52:1585&#x2013;1594.</Citation><ArticleIdList><ArticleId IdType="pubmed">15880817</ArticleId></ArticleIdList></Reference><Reference><Citation>Wente MN, Keane MP, Burdick MD, et al. Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis. Cancer Lett. 2006;241:221&#x2013;227.</Citation><ArticleIdList><ArticleId IdType="pubmed">16458421</ArticleId></ArticleIdList></Reference><Reference><Citation>Yin Y, Huang L, Zhao X, et al. AMD3100 mobilizes endothelial progenitor cells in mice, but inhibits its biological functions by blocking an autocrine/paracrine regulatory loop of stromal cell derived factor-1 in vitro. J Cardiovasc Pharmacol. 2007;50:61&#x2013;67.</Citation><ArticleIdList><ArticleId IdType="pubmed">17666917</ArticleId></ArticleIdList></Reference><Reference><Citation>Skotnicki JS, Zask A, Nelson FC, et al. Design and synthetic considerations of matrix metalloproteinase inhibitors. Ann NY Acad Sci. 1999;878:61&#x2013;72.</Citation><ArticleIdList><ArticleId IdType="pubmed">10415720</ArticleId></ArticleIdList></Reference><Reference><Citation>Goedkoop AY, Kraan MC, Picavet DI, et al. Deactivation of endothelium and reduction in angiogenesis in psoriatic skin and synovium by low dose infliximab therapy in combination with stable methotrexate therapy. Arthritis Res Ther. 2004;6:R326&#x2013;R334.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC464872</ArticleId><ArticleId IdType="pubmed">15225368</ArticleId></ArticleIdList></Reference><Reference><Citation>D&#x2019;Amato RJ, Loughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A. 1994;91:4082&#x2013;4085.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC43727</ArticleId><ArticleId IdType="pubmed">7513432</ArticleId></ArticleIdList></Reference><Reference><Citation>Ingber D, Fujita T, Kishimoto S, et al. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature. 1990;348:555&#x2013;557.</Citation><ArticleIdList><ArticleId IdType="pubmed">1701033</ArticleId></ArticleIdList></Reference><Reference><Citation>McCarey DW, Sattar N, McInnes IB. Do the pleiotropic effects of statins in the vasculature predict a role in inflammatory diseases? Arthritis Res Ther. 2005;7:55&#x2013;61.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1065332</ArticleId><ArticleId IdType="pubmed">15743490</ArticleId></ArticleIdList></Reference><Reference><Citation>Bongartz T, Coras B, Vogt T, et al. Treatment of active psoriatic arthritis with the PPAR&#x3b3; ligand pioglitazone: an open-label pilot study. Rheumatology. 2005;44:126&#x2013;129.</Citation><ArticleIdList><ArticleId IdType="pubmed">15479756</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">19945323</PMID><DateCompleted><Year>2010</Year><Month>02</Month><Day>25</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>20</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1778-7254</ISSN><JournalIssue CitedMedium="Internet"><Volume>76</Volume><Issue>6</Issue><PubDate><Year>2009</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Joint bone spine</Title><ISOAbbreviation>Joint Bone Spine</ISOAbbreviation></Journal><ArticleTitle>Endothelial progenitor cells in arthritis-associated vasculogenesis and atherosclerosis.</ArticleTitle><Pagination><StartPage>581</StartPage><EndPage>583</EndPage><MedlinePgn>581-3</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jbspin.2009.04.007</ELocationID><Abstract><AbstractText>Vasculogenesis is the generation of vessels from endothelial progenitor cells (EPCs). Attenuated numbers and function of EPCs associated with defective vasculogenesis are present in rheumatoid arthritis (RA), scleroderma and other autoimmune-inflammatory diseases, which have significant relevance for increased cardio- and cerebrovascular morbidity and mortality in arthritis [&#x2013;5]. Stimulation of EPCs and vasculogenesis may be beneficial to prevent and manage atherosclerosis related to arthritis. [&#x2013;5].</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>P&#xe1;kozdi</LastName><ForeName>Ang&#xe9;la</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Paragh</LastName><ForeName>Gy&#xf6;rgy</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Koch</LastName><ForeName>Alisa E</ForeName><Initials>AE</Initials></Author><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AR048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR048267-05</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016421">Editorial</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Joint Bone Spine</MedlineTA><NlmUniqueID>100938016</NlmUniqueID><ISSNLinking>1297-319X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000911">Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000911" MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050197" MajorTopicYN="N">Atherosclerosis</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015415" MajorTopicYN="N">Biomarkers</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004730" MajorTopicYN="N">Endothelium, Vascular</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045164" MajorTopicYN="N">Mesenchymal Stem Cell Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059630" MajorTopicYN="N">Mesenchymal Stem Cells</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009389" MajorTopicYN="N">Neovascularization, Pathologic</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013583" MajorTopicYN="N">Synovial Membrane</DescriptorName><QualifierName UI="Q000098" MajorTopicYN="N">blood supply</QualifierName></MeshHeading></MeshHeadingList><CoiStatement><b>Conflicts of interest</b>. The authors have no conflict of interest to declare.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2008</Year><Month>12</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2009</Year><Month>4</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>12</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>12</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>2</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2010</Year><Month>8</Month><Day>11</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">19945323</ArticleId><ArticleId IdType="mid">NIHMS222049</ArticleId><ArticleId IdType="pmc">PMC2919750</ArticleId><ArticleId IdType="doi">10.1016/j.jbspin.2009.04.007</ArticleId><ArticleId IdType="pii">S1297-319X(09)00187-0</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Freedman SB, Isner JM. Therapeutic angiogenesis for ischemic cardiovascular disease. J Mol Cell Cardiol. 2001;33:379&#x2013;93.</Citation><ArticleIdList><ArticleId IdType="pubmed">11181008</ArticleId></ArticleIdList></Reference><Reference><Citation>Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000;95:952&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">10648408</ArticleId></ArticleIdList></Reference><Reference><Citation>Shoenfeld Y, Gerli R, Doria A, et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005;112:3337&#x2013;47.</Citation><ArticleIdList><ArticleId IdType="pubmed">16301360</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Kerekes G, D&#xe9;r H, et al. Accelerated atherosclerosis in rheumatoid arthritis. Ann NY Acad Sci. 2007;1108:349&#x2013;58.</Citation><ArticleIdList><ArticleId IdType="pubmed">17893998</ArticleId></ArticleIdList></Reference><Reference><Citation>Grisar J, Aletaha D, Steiner CW, et al. Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis factor and glucocorticoid therapy. Ann Rheum Dis. 2007;66:1284&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1994291</ArticleId><ArticleId IdType="pubmed">17293363</ArticleId></ArticleIdList></Reference><Reference><Citation>Paleolog E. It&#x2019;s all in the blood: circulating endothelial progenitor cells link synovial vascularity with cardiovascular mortality in rheumatoid arthritis? Arthritis Res Ther. 2005;7:270&#x2013;2.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1297594</ArticleId><ArticleId IdType="pubmed">16277702</ArticleId></ArticleIdList></Reference><Reference><Citation>Avouac J, Uzan G, Kahan A, et al. Endothelial progenitor cells and rheumatic disorders. Joint Bone Spine. 2008;75:131&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pubmed">18314371</ArticleId></ArticleIdList></Reference><Reference><Citation>Gehling UM, Ergun S, Schumacher U, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000;95:3106&#x2013;12.</Citation><ArticleIdList><ArticleId IdType="pubmed">10807776</ArticleId></ArticleIdList></Reference><Reference><Citation>R&#xfc;ger B, Giurea A, Wanivenhaus AH, et al. Endothelial precursor cells in the synovial tissue of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum. 2004;50:2157&#x2013;66.</Citation><ArticleIdList><ArticleId IdType="pubmed">15248213</ArticleId></ArticleIdList></Reference><Reference><Citation>Silverman MD, Haas CS, Rad AM, et al. The role of vascular cell adhesion molecule 1/very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium. Arthritis Rheum. 2007;56:1817&#x2013;26.</Citation><ArticleIdList><ArticleId IdType="pubmed">17530710</ArticleId></ArticleIdList></Reference><Reference><Citation>Herbrig K, Haensel S, Oelschlaegel U, et al. Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann Rheum Dis. 2006;65:157&#x2013;63.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1798039</ArticleId><ArticleId IdType="pubmed">15975971</ArticleId></ArticleIdList></Reference><Reference><Citation>Petit I, Jin D, Rafii S. The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol. 2007;28:299&#x2013;307.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2952492</ArticleId><ArticleId IdType="pubmed">17560169</ArticleId></ArticleIdList></Reference><Reference><Citation>Ceradini DJ, Gurtner GC. Homing to hypoxia: HIF-1 as a mediator of progenitor cell recruitment to injured tissue. Trends Cardiovasc Med. 2005;15:57&#x2013;63.</Citation><ArticleIdList><ArticleId IdType="pubmed">15885571</ArticleId></ArticleIdList></Reference><Reference><Citation>Fan Y, Ye J, Shen F, et al. Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro. J Cereb Blood Flow Metab. 2008;28:90&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2581498</ArticleId><ArticleId IdType="pubmed">17519976</ArticleId></ArticleIdList></Reference><Reference><Citation>Oh IY, Yoon CH, Hur J, et al. Involvement of E-selectin in recruitment of endothelial progenitor cells and angiogenesis in ischemic muscle. Blood. 2007;110:3891&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pubmed">17699745</ArticleId></ArticleIdList></Reference><Reference><Citation>Akhavani MA, Larsen H, Paleolog E. Circulating endothelial progenitor cells link between synovial vascularity and cardiovascular mortality in rheumatoid arthritis. Scand J Rheumatol. 2007;36:83&#x2013;90.</Citation><ArticleIdList><ArticleId IdType="pubmed">17476612</ArticleId></ArticleIdList></Reference><Reference><Citation>Ablin JN, Boguslavski V, Aloush V, et al. Effect of anti-TNF&#x3b1; treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis. Life Sci. 2006;79:2364&#x2013;9.</Citation><ArticleIdList><ArticleId IdType="pubmed">16962143</ArticleId></ArticleIdList></Reference><Reference><Citation>Jacobsson LT, Turesson C, G&#xfc;lfe A, et al. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol. 2005;32:1213&#x2013;8.</Citation><ArticleIdList><ArticleId IdType="pubmed">15996054</ArticleId></ArticleIdList></Reference><Reference><Citation>Dixon WG, Watson KD, Lunt M, et al. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 2007;56:2905&#x2013;12.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2435427</ArticleId><ArticleId IdType="pubmed">17763428</ArticleId></ArticleIdList></Reference><Reference><Citation>Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pubmed">9020076</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">19863375</PMID><DateCompleted><Year>2010</Year><Month>01</Month><Day>11</Day></DateCompleted><DateRevised><Year>2022</Year><Month>03</Month><Day>17</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1607-842X</ISSN><JournalIssue CitedMedium="Internet"><Volume>42</Volume><Issue>7</Issue><PubDate><Year>2009</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Autoimmunity</Title><ISOAbbreviation>Autoimmunity</ISOAbbreviation></Journal><ArticleTitle>Angiogenesis in rheumatoid arthritis.</ArticleTitle><Pagination><StartPage>563</StartPage><EndPage>573</EndPage><MedlinePgn>563-73</MedlinePgn></Pagination><Abstract><AbstractText>Angiogenesis is the formation of new capillaries from pre-existing vessels. A number of soluble and cell-bound factors may stimulate neovascularization. The perpetuation of angiogenesis involving numerous soluble and cell surface-bound mediators has been associated with rheumatoid arthritis (RA). These angiogenic mediators, among others, include growth factors, primarily vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as pro-inflammatory cytokines, various chemokines, matrix components, cell adhesion molecules, proteases and others. Among the several potential angiogenesis inhibitors, targeting of VEGF, HIF-1, angiogenic chemokines, tumor necrosis factor-alpha and the alpha(V)beta(3) integrin may attenuate the action of angiogenic mediators and thus synovial angiogenesis. In addition, some naturally produced or synthetic compounds including angiostatin, endostatin, paclitaxel, fumagillin analogues, 2-methoxyestradiol and thalidomide may be included in the management of RA.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Rheumatology, Institute of Medicine, University of Debrecen Medical and Health Sciences Center, Debrecen, H-4032, Hungary. szekanecz.zoltan@med.unideb.hu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Paragh</LastName><ForeName>Gy&#xf6;rgy</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Koch</LastName><ForeName>Alisa E</ForeName><Initials>AE</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI040987-08</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI040987</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR-048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR048267-05</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Autoimmunity</MedlineTA><NlmUniqueID>8900070</NlmUniqueID><ISSNLinking>0891-6934</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D020533">Angiogenesis Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015815">Cell Adhesion Molecules</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018836">Inflammation Mediators</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019707">Receptors, Chemokine</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D042461">Vascular Endothelial Growth Factor A</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D020533" MajorTopicYN="N">Angiogenesis Inhibitors</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001808" MajorTopicYN="N">Blood Vessels</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015815" MajorTopicYN="N">Cell Adhesion Molecules</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005109" MajorTopicYN="N">Extracellular Matrix</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018836" MajorTopicYN="N">Inflammation Mediators</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009389" MajorTopicYN="N">Neovascularization, Pathologic</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019707" MajorTopicYN="N">Receptors, Chemokine</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D042461" MajorTopicYN="N">Vascular Endothelial Growth Factor A</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>10</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>10</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>1</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2010</Year><Month>8</Month><Day>9</Day></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">19863375</ArticleId><ArticleId IdType="mid">NIHMS222118</ArticleId><ArticleId IdType="pmc">PMC2917919</ArticleId><ArticleId IdType="doi">10.1080/08916930903143083</ArticleId><ArticleId IdType="pii">10.1080/08916930903143083</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Koch AE. Angiogenesis: Implications for rheumatoid arthritis. Arthritis Rheum. 1998;41:951&#x2013;962.</Citation><ArticleIdList><ArticleId IdType="pubmed">9627005</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Endothelial cells in inflammation and angiogenesis. Curr Drug Targ. 2005;4:319&#x2013;323.</Citation><ArticleIdList><ArticleId IdType="pubmed">16101540</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Vascular involvement in rheumatic diseases: &#x2018;vascular rheumatology&#x2019;. Arthritis Res Ther. 2008;10:224.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2592799</ArticleId><ArticleId IdType="pubmed">18947376</ArticleId></ArticleIdList></Reference><Reference><Citation>Foster W, Carruthers D, Lip GY, Blann AD. Relationship between endothelial inflammatory and angiogenesis markers in rheumatoid arthritis: Implications for cardiovascular pathophysiology. Thromb Res. 2009;4:659&#x2013;664.</Citation><ArticleIdList><ArticleId IdType="pubmed">18692223</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Mechanism of disease: Angiogenesis in inflammatory diseases. Nat Clin Pract Rheumatol. 2007;3:635&#x2013;643.</Citation><ArticleIdList><ArticleId IdType="pubmed">17968334</ArticleId></ArticleIdList></Reference><Reference><Citation>Lainer-Carr D, Brahn E. Angiogenesis inhibition as a therapeutic approach for inflammatory synovitis. Nat Clin Pract Rheumatol. 2007;3:434&#x2013;442.</Citation><ArticleIdList><ArticleId IdType="pubmed">17664950</ArticleId></ArticleIdList></Reference><Reference><Citation>Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;235:442&#x2013;447.</Citation><ArticleIdList><ArticleId IdType="pubmed">2432664</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Chemokines and angiogenesis. Curr Opin Rheumatol. 2001;13:202&#x2013;208.</Citation><ArticleIdList><ArticleId IdType="pubmed">11333349</ArticleId></ArticleIdList></Reference><Reference><Citation>Naumov GN, Folkman J, Straume O, Akslen LA. Tumor-vascular interactions and tumor dormancy. APMIS. 2008;116:569&#x2013;585.</Citation><ArticleIdList><ArticleId IdType="pubmed">18834403</ArticleId></ArticleIdList></Reference><Reference><Citation>Shams N, Ianchulev T. Role of vascular endothelial growth factor in ocular angiogenesis. Ophthalmol Clin North Am. 2006;19:335&#x2013;344.</Citation><ArticleIdList><ArticleId IdType="pubmed">16935208</ArticleId></ArticleIdList></Reference><Reference><Citation>Jakobsson L, Claesson-Welsh L. Vascular basement membrane components in angiogenesis&#x2014;an act of balance. Sci World J. 2008;8:1246&#x2013;1249.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC5848701</ArticleId><ArticleId IdType="pubmed">19082420</ArticleId></ArticleIdList></Reference><Reference><Citation>Veale DJ, Fearon U. Inhibition of angiogenic pathways in rheumatoid arthritis: Potential for therapeutic targeting. Best Pract Res Clin Rheumatol. 2006;20:941&#x2013;947.</Citation><ArticleIdList><ArticleId IdType="pubmed">16980216</ArticleId></ArticleIdList></Reference><Reference><Citation>Agarwal SK, Brenner MB. Role of adhesion molecules in synovial inflammation. Curr Opin Rheumatol. 2006;18:268&#x2013;276.</Citation><ArticleIdList><ArticleId IdType="pubmed">16582691</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Macrophages and their products in rheumatoid arthritis. Curr Opin Rheumatol. 2007;19:289&#x2013;295.</Citation><ArticleIdList><ArticleId IdType="pubmed">17414958</ArticleId></ArticleIdList></Reference><Reference><Citation>Koch AE, Harlow LA, Haines GK, Amento EP, Unemori EN, Wong WL, Pope RM, Ferrara N. Vascular endothelial growth factor. A cytokine modulating endothelial function in rheumatoid arthritis. J Immunol. 1994;152:4149&#x2013;4156.</Citation><ArticleIdList><ArticleId IdType="pubmed">7511670</ArticleId></ArticleIdList></Reference><Reference><Citation>Kiselyov A, Balakin KV, Tkachenko SE. VEGF/VEGFR signaling as a target for inhibiting angiogenesis. Expert Opin Investig Drugs. 2007;16:83&#x2013;107.</Citation><ArticleIdList><ArticleId IdType="pubmed">17155856</ArticleId></ArticleIdList></Reference><Reference><Citation>Shibuya M. Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis. BMB Rep. 2008;41:278&#x2013;286.</Citation><ArticleIdList><ArticleId IdType="pubmed">18452647</ArticleId></ArticleIdList></Reference><Reference><Citation>Hernandez GL, Volpert OV, I&#xf1;iguez MA, Lorenzo E, Mart&#xed;nez-Mart&#xed;nez S, Grau R, Fresno M, Redondo JM. Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: Roles of the nuclear factor of activated T cells and cyclooxygenase 2. J Exp Med. 2001;193:607&#x2013;612.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2193389</ArticleId><ArticleId IdType="pubmed">11238591</ArticleId></ArticleIdList></Reference><Reference><Citation>Taylor PC, Sivakumar B. Hypoxia and angiogenesis in rheumatoid arthritis. Curr Opin Rheumatol. 2005;17:293&#x2013;298.</Citation><ArticleIdList><ArticleId IdType="pubmed">15838239</ArticleId></ArticleIdList></Reference><Reference><Citation>Amin MA, Mansfield PJ, Pakozdi A, Campbell PL, Ahmed S, Martinez RJ, Koch AE. Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways. Arthritis Rheum. 2007;56:1787&#x2013;1797.</Citation><ArticleIdList><ArticleId IdType="pubmed">17530707</ArticleId></ArticleIdList></Reference><Reference><Citation>Kim HR, Park MK, Cho ML, Yoon CH, Lee SH, Park SH, Leng L, Bucala R, Kang I, Choe J, Kim HY. Macrophage migration inhibitory factor upregulates angiogenic factors and correlates with clinical measures in rheumatoid arthritis. J Rheumatol. 2007;34:927&#x2013;936.</Citation><ArticleIdList><ArticleId IdType="pubmed">17407222</ArticleId></ArticleIdList></Reference><Reference><Citation>Koch AE, Distler O. Vasculopathy and disordered angiogenesis in selected rheumatic diseases: Rheumatoid arthritis and systemic sclerosis. Arthritis Res Ther. 2007;9(Suppl. 2):S3.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2072889</ArticleId><ArticleId IdType="pubmed">17767741</ArticleId></ArticleIdList></Reference><Reference><Citation>Haq A, El-Ramahi K, Al-Dalaan A. Serum and synovial fluid concentrations of endothelin-1 in patients with inflammatory arthritides. J Med. 1999;30:51&#x2013;60.</Citation><ArticleIdList><ArticleId IdType="pubmed">10515240</ArticleId></ArticleIdList></Reference><Reference><Citation>Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS. VEGF-Trap: A VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 2002;99:11393&#x2013;11398.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC123267</ArticleId><ArticleId IdType="pubmed">12177445</ArticleId></ArticleIdList></Reference><Reference><Citation>Manley PW, Martiny-Baron G, Schlaeppi JM, Wood JM. Therapies directed at vascular endothelial growth factor. Expert Opin Investig Drugs. 2002;11:1715&#x2013;1736.</Citation><ArticleIdList><ArticleId IdType="pubmed">12457433</ArticleId></ArticleIdList></Reference><Reference><Citation>Grosios K, Wood J, Esser R, Raychaudhuri A, Dawson J. Angiogenesis inhibition by the novel VEGF tyrosine kinase inhibitor, PTK787/ZK222584, causes significant anti-arthritic effects in models of rheumatoid arthritis. Inflamm Res. 2004;53:133&#x2013;142.</Citation><ArticleIdList><ArticleId IdType="pubmed">15060719</ArticleId></ArticleIdList></Reference><Reference><Citation>Kim WU, Kwok SK, Hong KH, Yoo SA, Kong JS, Choe J, Cho CS. Soluble Fas ligand inhibits angiogenesis in rheumatoid arthritis. Arthritis Res Ther. 2007;26:R42.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1906820</ArticleId><ArticleId IdType="pubmed">17459170</ArticleId></ArticleIdList></Reference><Reference><Citation>Choi ST, Kim JH, Seok JY, Park YB, Lee SK. Therapeutic effect of anti-vascular endothelial growth factor receptor I antibody in the established collagen-induced arthritis mouse model. Clin Rheumatol. 2009;3:333&#x2013;337.</Citation><ArticleIdList><ArticleId IdType="pubmed">19101756</ArticleId></ArticleIdList></Reference><Reference><Citation>Guttmann-Raviv N, Shraga-Heled N, Varshavsky A, Guimaraes-Sternberg C, Kessler O, Neufeld G. Semaphorin-3A and semaphorin-3F work together to repel endothelial cells and to inhibit their survival by induction of apoptosis. J Biol Chem. 2007;282:26294&#x2013;26305.</Citation><ArticleIdList><ArticleId IdType="pubmed">17569671</ArticleId></ArticleIdList></Reference><Reference><Citation>Fearon U, Veale DJ. Angiogenesis in arthritis: Methodological and analytical details. Methods Mol Med. 2007;135:343&#x2013;357.</Citation><ArticleIdList><ArticleId IdType="pubmed">17951670</ArticleId></ArticleIdList></Reference><Reference><Citation>Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter KC, Harris AL, Koukourakis MI. Upregulated hypoxia inducible factor-1&#x3b1; and -2&#x3b1; pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2003;5:R193&#x2013;R198.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC165055</ArticleId><ArticleId IdType="pubmed">12823854</ArticleId></ArticleIdList></Reference><Reference><Citation>Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, Baek KH, Rosenzweig A, Spiegelman BM. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature. 2008;451:1008&#x2013;1012.</Citation><ArticleIdList><ArticleId IdType="pubmed">18288196</ArticleId></ArticleIdList></Reference><Reference><Citation>Aljada A, O'Connor L, Fu YY, Mousa SA. PPAR&#x3b3; ligands, rosiglitazone and pioglitazone inhibit bFGF- and VEGF-mediated angiogenesis. Angiogenesis. 2008;11:361&#x2013;367.</Citation><ArticleIdList><ArticleId IdType="pubmed">18810647</ArticleId></ArticleIdList></Reference><Reference><Citation>Bongartz T, Coras B, Vogt T, Sch&#xf6;lmerich J, M&#xfc;ller-Ladner U. Treatment of active psoriatic arthritis with the PPAR&#x3b3; ligand pioglitazone: An open-label pilot study. Rheumatology. 2005;44:126&#x2013;129.</Citation><ArticleIdList><ArticleId IdType="pubmed">15479756</ArticleId></ArticleIdList></Reference><Reference><Citation>Piqueras L, Reynolds AR, Hodivala-Dilke KM, Alfranca A, Redondo JM, Hatae T, Tanabe T, Warner TD, Bishop-Bailey D. Activation of PPAR&#x3b2;/&#x3b4; induces endothelial cell proliferation and angiogenesis. Arterioscler Thromb Vasc Biol. 2007;27:63&#x2013;69.</Citation><ArticleIdList><ArticleId IdType="pubmed">17068288</ArticleId></ArticleIdList></Reference><Reference><Citation>Yeo EJ, Chun YS, Cho YS, Kim J, Lee JC, Kim MS, Park JW. YC-1: A potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst. 2003;95:516&#x2013;525.</Citation><ArticleIdList><ArticleId IdType="pubmed">12671019</ArticleId></ArticleIdList></Reference><Reference><Citation>Hirota SA, Beck PL, MacDonald JA. Targeting hypoxia-inducible factor-1 (HIF-1) signaling in therapeutics: Implications for the treatment of inflammatory bowel disease. Recent Pat Inflamm Allergy Drug Discov. 2009;3:1&#x2013;16.</Citation><ArticleIdList><ArticleId IdType="pubmed">19149741</ArticleId></ArticleIdList></Reference><Reference><Citation>Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD, Wiegand SJ. Vessel cooption, regression and growth in tumors mediated by angiopoietins and VEGF. Science. 1999;284:1994&#x2013;1998.</Citation><ArticleIdList><ArticleId IdType="pubmed">10373119</ArticleId></ArticleIdList></Reference><Reference><Citation>Gravallese EM, Pettit AR, Lee R, Madore R, Manning C, Tsay A, Gaspar J, Goldring MB, Goldring SR, Oettgen P. Angiopoietin-1 is expressed in the synovium of patients with rheumatoid arthritis and is induced by tumour necrosis factor alpha. Ann Rheum Dis. 2003;62:100&#x2013;107.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1754433</ArticleId><ArticleId IdType="pubmed">12525377</ArticleId></ArticleIdList></Reference><Reference><Citation>Tran J, Master Z, Yu JL, Rak J, Dumont DJ, Kerbel RS. A role for surviving in chemoresistance of endothelial cells mediated by VEGF. Proc Natl Acad Sci USA. 2002;99:4349&#x2013;4354.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC123651</ArticleId><ArticleId IdType="pubmed">11917134</ArticleId></ArticleIdList></Reference><Reference><Citation>Shahrara S, Volin MV, Connors MA, Haines GK, Koch AE. Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue. Arthritis Res. 2002;4:201&#x2013;208.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC111023</ArticleId><ArticleId IdType="pubmed">12010571</ArticleId></ArticleIdList></Reference><Reference><Citation>Chen Y, Donnelly E, Kobayashi H, Debusk LM, Lin PC. Gene therapy targeting the Tie2 function ameliorates collagen-induced arthritis and protects against bone destruction. Arthritis Rheum. 2005;52:1585&#x2013;1594.</Citation><ArticleIdList><ArticleId IdType="pubmed">15880817</ArticleId></ArticleIdList></Reference><Reference><Citation>Yoo SA, Yoon HJ, Kim HS, Chae CB, De Falco S, Cho CS, Kim WU. Role of placenta growth factor and its receptor flt-1 in rheumatoid inflammation: A link between angiogenesis and inflammation. Arthritis Rheum. 2009;60:345&#x2013;354.</Citation><ArticleIdList><ArticleId IdType="pubmed">19180491</ArticleId></ArticleIdList></Reference><Reference><Citation>Kameda H, Ishigami H, Suzuki M, Abe T, Takeuchi T. Imatinib mesylate inhibits proliferation of rheumatoid synovial fibroblast-like cells and phosphorylation of Gab adapter proteins activated by platelet-derived growth factors. Clin Exp Immunol. 2006;144:335&#x2013;341.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1809657</ArticleId><ArticleId IdType="pubmed">16634808</ArticleId></ArticleIdList></Reference><Reference><Citation>Koyama K, Hatsushika K, Ando T, Sakuma M, Wako M, Kato R, Haro H, Sugiyama H, Hamada Y, Ogawa H, Nakao A. Imatinib mesylate both prevents and treats the arthritis induced by type II collagen antibody in mice. Mod Rheumatol. 2007;17:306&#x2013;310.</Citation><ArticleIdList><ArticleId IdType="pubmed">17694264</ArticleId></ArticleIdList></Reference><Reference><Citation>Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, Dzuiba J, Van Damme J, Walz A, Marriott D, Chan S-Y, Roczniak S, Shanafelt AB. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995;270:27348&#x2013;27357.</Citation><ArticleIdList><ArticleId IdType="pubmed">7592998</ArticleId></ArticleIdList></Reference><Reference><Citation>Petit I, Jin D, Rafii S. The SDF-1-CXCR4 signaling pathway: A molecular hub modulating neo-angiogenesis. Trends Immunol. 2007;28:299&#x2013;307.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2952492</ArticleId><ArticleId IdType="pubmed">17560169</ArticleId></ArticleIdList></Reference><Reference><Citation>Pablos JL, Santiago B, Galindo M, Torres C, Brehmer M, Blanco FJ, Garcia-Lazaro FJ. Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. J Immunol. 2003;170:2147&#x2013;2152.</Citation><ArticleIdList><ArticleId IdType="pubmed">12574387</ArticleId></ArticleIdList></Reference><Reference><Citation>Calatozzolo C, Maderna E, Pollo B, Gelati M, Marras C, Silvani A, Croci D, Boiardi A, Salmaggi A. Prognostic value of CXCL12 expression in 40 low-grade oligodendrogliomas and oligoastrocytomas. Cancer Biol Ther. 2006;5:827&#x2013;832.</Citation><ArticleIdList><ArticleId IdType="pubmed">16760646</ArticleId></ArticleIdList></Reference><Reference><Citation>Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK, Oppenheim JJ, Murphy WJ. Human endothelial cells express CCR2 and respond to MCP-1: Direct role of MCP-1 in angiogenesis and tumor progression. Blood. 2000;96:34&#x2013;40.</Citation><ArticleIdList><ArticleId IdType="pubmed">10891427</ArticleId></ArticleIdList></Reference><Reference><Citation>Stamatovic SM, Keep RF, Mostarica-Stojkovic M, Andjelkovic AV. CCL2 regulates angiogenesis via activation of Ets-1 transcription factor. J Immunol. 2006;177:2651&#x2013;2661.</Citation><ArticleIdList><ArticleId IdType="pubmed">16888027</ArticleId></ArticleIdList></Reference><Reference><Citation>Volin MV, Woods JM, Amin MA, Connors MA, Harlow LA, Koch AE. Fractalkine: A novel angiogenic chemokine in rheumatoid arthritis. Am J Pathol. 2001;159:1521&#x2013;1526.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1850492</ArticleId><ArticleId IdType="pubmed">11583978</ArticleId></ArticleIdList></Reference><Reference><Citation>Nanki T, Hayashida K, El-Gabalawy HS, Suson S, Shi K, Girschick HJ, Yavuz S, Lipsky PE. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4 + T-cell accumulation in rheumatoid arthritis synovium. J Immunol. 2000;165:6590&#x2013;6598.</Citation><ArticleIdList><ArticleId IdType="pubmed">11086103</ArticleId></ArticleIdList></Reference><Reference><Citation>Wente MN, Keane MP, Burdick MD, Friess H, B&#xfc;chler MW, Ceyhan GO, Reber HA, Strieter RM, Hines OJ. Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis. Cancer Lett. 2006;241:221&#x2013;227.</Citation><ArticleIdList><ArticleId IdType="pubmed">16458421</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang R, Tian L, Chen LJ, Hou JM, Li G, Li J, Zhang L, Chen XC, Luo F, Jiang Y, Wei YQ. Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma. Gene Ther. 2006;13:1263&#x2013;1271.</Citation><ArticleIdList><ArticleId IdType="pubmed">16672984</ArticleId></ArticleIdList></Reference><Reference><Citation>Yin Y, Huang L, Zhao X, Fang Y, Yu S, Zhao J, Cui B. AMD3100 mobilizes endothelial progenitor cells in mice, but inhibits its biological functions by blocking an autocrine/paracrine regulatory loop of stromal cell derived factor-1 in vitro. J Cardiovasc Pharmacol. 2007;50:61&#x2013;67.</Citation><ArticleIdList><ArticleId IdType="pubmed">17666917</ArticleId></ArticleIdList></Reference><Reference><Citation>Madri JA, Williams KS. Capillary endothelial cell cultures: Phenotypic modulation by matrix components. J Cell Biol. 1983;97:153&#x2013;165.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2112496</ArticleId><ArticleId IdType="pubmed">6190818</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Szegedi G, Koch AE. Cellular adhesion molecules in rheumatoid arthritis. Regulation by cytokines and possible clinical importance. J Investig Med. 1996;44:124&#x2013;135.</Citation><ArticleIdList><ArticleId IdType="pubmed">8689407</ArticleId></ArticleIdList></Reference><Reference><Citation>Imhof BA, Aurrand-Lions M. Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol. 2004;4:432&#x2013;444.</Citation><ArticleIdList><ArticleId IdType="pubmed">15173832</ArticleId></ArticleIdList></Reference><Reference><Citation>Koch AE, Halloran MM, Haskell CJ, Shah MR, Polverini PJ. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature. 1995;376:517&#x2013;519.</Citation><ArticleIdList><ArticleId IdType="pubmed">7543654</ArticleId></ArticleIdList></Reference><Reference><Citation>Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994;264:569&#x2013;571.</Citation><ArticleIdList><ArticleId IdType="pubmed">7512751</ArticleId></ArticleIdList></Reference><Reference><Citation>Huang MT, Mason JC, Birdsey GM, Amsellem V, Gerwin N, Haskard DO, Ridley AJ, Randi AM. Endothelial intercellular adhesion molecule (ICAM)-2 regulates angiogenesis. Blood. 2005;106:1636&#x2013;1643.</Citation><ArticleIdList><ArticleId IdType="pubmed">15920013</ArticleId></ArticleIdList></Reference><Reference><Citation>Naik TU, Naik MU, Naik UP. Junctional adhesion molecules in angiogenesis. Front Biosci. 2008;13:258&#x2013;262.</Citation><ArticleIdList><ArticleId IdType="pubmed">17981544</ArticleId></ArticleIdList></Reference><Reference><Citation>Rabquer BJ, Pakozdi A, Michel JE, Gujar BS, Haines GK, III, Imhof BA, Koch AE. Junctional adhesion molecule C mediates leukocyte adhesion to rheumatoid arthritis synovium. Arthritis Rheum. 2008;58:3020&#x2013;3039.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2911024</ArticleId><ArticleId IdType="pubmed">18821692</ArticleId></ArticleIdList></Reference><Reference><Citation>Jacq L, Garnier S, Dieud&#xe9; P, Michou L, Pierlot C, Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Vaz C, Fernandes M, Pascual-Salcedo D, Bombardieri S, Dequeker J, Radstake TR, Van Riel P, van de Putte L, Lopes-Vaz A, Glikmans E, Barbet S, Lasbleiz S, Lemaire I, Quillet P, Hilliquin P, Teixeira VH, Petit-Teixeira E, Mbarek H, Prum B, Bardin T, Corn&#xe9;lis F. European Consortium on Rheumatoid Arthritis Families. The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: A family-based study. Arthritis Res Ther. 2007;9:R63.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2206364</ArticleId><ArticleId IdType="pubmed">17615072</ArticleId></ArticleIdList></Reference><Reference><Citation>Shahrara S, Castro-Rueda HP, Haines GK, Koch AE. Differential expression of the FAK family kinases in rheumatoid arthritis and osteoarthritis synovial tissues. Arthritis Res Ther. 2007;9:R112.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2212559</ArticleId><ArticleId IdType="pubmed">17963503</ArticleId></ArticleIdList></Reference><Reference><Citation>Kneilling M, H&#xfc;ltner L, Pichler BJ, Mailhammer R, Morawietz L, Solomon S, Eichner M, Sabatino J, Biedermann T, Krenn V, Weber WA, Illges H, Haubner R, R&#xf6;cken M. Targeted mast cell silencing protects against joint destruction and angiogenesis in experimental arthritis in mice. Arthritis Rheum. 2007;56:1806&#x2013;1816.</Citation><ArticleIdList><ArticleId IdType="pubmed">17530709</ArticleId></ArticleIdList></Reference><Reference><Citation>McCarey DW, Sattar N, McInnes IB. Do the pleiotropic effects of statins in the vasculature predict a role in inflammatory diseases? Arthritis Res Ther. 2005;7:55&#x2013;61.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1065332</ArticleId><ArticleId IdType="pubmed">15743490</ArticleId></ArticleIdList></Reference><Reference><Citation>Skotnicki JS, Zask A, Nelson FC, Albright JD, Levin JI. Design and synthetic considerations of matrix metalloproteinase inhibitors. Ann NY Acad Sci. 1999;878:61&#x2013;72.</Citation><ArticleIdList><ArticleId IdType="pubmed">10415720</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Strieter RM, Koch AE. Cytokines in rheumatoid arthritis: Potential targets for pharmacological intervention. Drugs Aging. 1998;12:377&#x2013;390.</Citation><ArticleIdList><ArticleId IdType="pubmed">9606615</ArticleId></ArticleIdList></Reference><Reference><Citation>Brennan F, Beech J. Update on cytokines in rheumatoid arthritis. Curr Opin Rheumatol. 2007;19:296&#x2013;301.</Citation><ArticleIdList><ArticleId IdType="pubmed">17414959</ArticleId></ArticleIdList></Reference><Reference><Citation>Park CC, Morel JC, Amin MA, Connors MA, Harlow LA, Koch AE. Evidence of IL-18 as a novel angiogenic mediator. J Immunol. 2001;167:1644&#x2013;1653.</Citation><ArticleIdList><ArticleId IdType="pubmed">11466388</ArticleId></ArticleIdList></Reference><Reference><Citation>Angiolillo AL, Kanegane H, Sgadari C, Reaman GH, Tosato G. Interleukin15 promotes angiogenesis in vivo. Biochem Biophys Res Commun. 1997;233:231&#x2013;237.</Citation><ArticleIdList><ArticleId IdType="pubmed">9144429</ArticleId></ArticleIdList></Reference><Reference><Citation>Leibovich SJ, Polverini PJ, Shepard HM, Wiseman DM, Shively V, Nuseir N. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-&#x3b1;. Nature. 1987;329:630&#x2013;632.</Citation><ArticleIdList><ArticleId IdType="pubmed">2443857</ArticleId></ArticleIdList></Reference><Reference><Citation>Markham T, Mullan R, Golden-Mason L, Rogers S, Bresnihan B, Fitzgerald O, Fearon U, Veale DJ. Resolution of endothelial activation and down-regulation of Tie2 receptor in psoriatic skin after infliximab therapy. J Am Acad Dermatol. 2006;54:1003&#x2013;1012.</Citation><ArticleIdList><ArticleId IdType="pubmed">16713454</ArticleId></ArticleIdList></Reference><Reference><Citation>Nakahara H, Song J, Sugimoto M, Hagihara K, Kishimoto T, Yoskizaki K, Nishimoto N. Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthritis Rheum. 2003;48:1521&#x2013;1529.</Citation><ArticleIdList><ArticleId IdType="pubmed">12794819</ArticleId></ArticleIdList></Reference><Reference><Citation>Numasaki M, Watanabe M, Suzuki T, Takahashi H, Nakamura A, McAllister F, Hishinuma T, Goto J, Lotze MT, Kolls JK, Sasaki H. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR2-dependent angiogenesis. J Immunol. 2005;175:6177&#x2013;6189.</Citation><ArticleIdList><ArticleId IdType="pubmed">16237115</ArticleId></ArticleIdList></Reference><Reference><Citation>Fearon U, Mullan R, Markham T, Connolly M, Sullivan S, Poole AR, FitzGerald O, Bresnihan B, Veale DJ. Oncostatin M induces angiogenesis and cartilage degradation in rheumatoid arthritis synovial tissue and human cartilage cocultures. Arthritis Rheum. 2006;54:3152&#x2013;3162.</Citation><ArticleIdList><ArticleId IdType="pubmed">17009243</ArticleId></ArticleIdList></Reference><Reference><Citation>Amin MA, Volpert OV, Woods JM, Kumar P, Harlow LA, Koch AE. Migration inhibitory factor mediates angiogenesis via mitogen-activated protein kinase and phosphatidylinositol kinase. Circ Res. 2003;93:321&#x2013;329.</Citation><ArticleIdList><ArticleId IdType="pubmed">12881477</ArticleId></ArticleIdList></Reference><Reference><Citation>Morand EF, Leech M, Bernhagen J. MIF: A new cytokine link between rheumatoid arthritis and atherosclerosis. Nat Rev Drug Discov. 2006;5:399&#x2013;410.</Citation><ArticleIdList><ArticleId IdType="pubmed">16628200</ArticleId></ArticleIdList></Reference><Reference><Citation>Goedkoop AY, Kraan MC, Picavet DI, de Rie MA, Teunissen MB, Bos JD, Tak PP. Deactivation of endothelium and reduction in angiogenesis in psoriatic skin and synovium by low dose infliximab therapy in combination with stable methotrexate therapy. Arthritis Res Ther. 2004;6:R326&#x2013;R334.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC464872</ArticleId><ArticleId IdType="pubmed">15225368</ArticleId></ArticleIdList></Reference><Reference><Citation>Dessein PH, Joffe BI. Suppression of circulating interleukin-6 concentrations is associated with decreased endothelial activation in rheumatoid arthritis. Clin Exp Rheumatol. 2006;24:161&#x2013;167.</Citation><ArticleIdList><ArticleId IdType="pubmed">16762151</ArticleId></ArticleIdList></Reference><Reference><Citation>Koch AE, Distler O. Vasculopathy and disordered angiogenesis in selected rheumatic diseases: Rheumatoid arthritis and systemic sclerosis. Arthritis Res Ther. 2007;9(Suppl. 2):S3.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2072889</ArticleId><ArticleId IdType="pubmed">17767741</ArticleId></ArticleIdList></Reference><Reference><Citation>Haq A, El-Ramahi K, Al-Dalaan A. Serum and synovial fluid concentrations of endothelin-1 in patients with inflammatory arthritides. J Med. 1999;30:51&#x2013;60.</Citation><ArticleIdList><ArticleId IdType="pubmed">10515240</ArticleId></ArticleIdList></Reference><Reference><Citation>Lee MS, Yoo SA, Cho CS, Suh PG, Kim WU, Ryu SH. Serum amyloid A binding to formyl peptide receptor-like 1 induces synovial hyperplasia and angiogenesis. J Immunol. 2006;177:5585&#x2013;5594.</Citation><ArticleIdList><ArticleId IdType="pubmed">17015746</ArticleId></ArticleIdList></Reference><Reference><Citation>Mullan RH, Bresnihan B, Golden-Mason L, Markham T, O'Hara R, FitzGerald O, Veale DJ, Fearon U. Acute-phase serum amyloid A stimulation of angiogenesis, leukocyte recruitment and matrix degradation in rheumatoid arthritis through an NF-&#x3ba;B-dependent signal transduction pathway. Arthritis Rheum. 2006;54:105&#x2013;114.</Citation><ArticleIdList><ArticleId IdType="pubmed">16385502</ArticleId></ArticleIdList></Reference><Reference><Citation>Hong KH, Cho ML, Min SY, Shin YJ, Yoo SA, Choi JJ, Kim WU, Song SW, Cho CS. Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid synovial fibroblasts. Clin Exp Immunol. 2007;147:573&#x2013;579.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1810499</ArticleId><ArticleId IdType="pubmed">17302909</ArticleId></ArticleIdList></Reference><Reference><Citation>Haas CS, Amin MA, Allen BB, Ruth JH, Haines GK, III, Woods JM, Koch AE. Inhibition of angiogenesis by interleukin-4 gene therapy in rat adjuvant-induced arthritis. Arthritis Rheum. 2006;54:2402&#x2013;2414.</Citation><ArticleIdList><ArticleId IdType="pubmed">16869003</ArticleId></ArticleIdList></Reference><Reference><Citation>Haas CS, Amin MA, Ruth JH, Allen BL, Ahmed S, Pakozdi A, Woods JM, Shahrara S, Koch AE. In vivo inhibition of angiogenesis by interleukin-13 gene therapy in a rat model of rheumatoid arthritis. Arthritis Rheum. 2007;56:2535&#x2013;2548.</Citation><ArticleIdList><ArticleId IdType="pubmed">17665443</ArticleId></ArticleIdList></Reference><Reference><Citation>Boulday G, Haskova Z, Reinders ME, Pal S, Briscoe DM. Vascular endothelial growth factor-induced signaling pathways in endothelial cells that mediate overexpression of the chemokine IFN-gamma-inducible protein of 10 kDa in vitro and in vivo. J Immunol. 2006;176:3098&#x2013;3107.</Citation><ArticleIdList><ArticleId IdType="pubmed">16493069</ArticleId></ArticleIdList></Reference><Reference><Citation>Maurer AM, Zhou B, Han ZC. Roles of platelet factor 4 in hematopoiesis and angiogenesis. Growth Factors. 2006;24:242&#x2013;252.</Citation><ArticleIdList><ArticleId IdType="pubmed">17381065</ArticleId></ArticleIdList></Reference><Reference><Citation>Vicari AP, Ait-Yahia S, Chemin K, Mueller A, Zlotnik A, Caux C. Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and immunological mechanisms. J Immunol. 2000;165:1992&#x2013;2000.</Citation><ArticleIdList><ArticleId IdType="pubmed">10925282</ArticleId></ArticleIdList></Reference><Reference><Citation>Woods JM, Mogollon A, Amin MA, Martinez RJ, Koch AE. The role of COX-2 in angiogenesis and rheumatoid arthritis. Exp Mol Pathol. 2003;74:282&#x2013;290.</Citation><ArticleIdList><ArticleId IdType="pubmed">12782016</ArticleId></ArticleIdList></Reference><Reference><Citation>D'Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA. 1994;91:4082&#x2013;4085.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC43727</ArticleId><ArticleId IdType="pubmed">7513432</ArticleId></ArticleIdList></Reference><Reference><Citation>Komorowski J, Jerczy&#x144;ska H, Siejka A, Bara&#x144;ska P, &#x141;awnicka H, Paw&#x142;owska Z, Stepie&#x144; H. Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA.hy926 cells. Life Sci. 2006;78:2558&#x2013;2663.</Citation><ArticleIdList><ArticleId IdType="pubmed">16310808</ArticleId></ArticleIdList></Reference><Reference><Citation>Oliver SJ, Cheng TP, Banquerigo ML, Brahn E. The effect of thalidomide and two analogs on collagen induced arthritis. J Rheumatol. 1998;25:964&#x2013;969.</Citation><ArticleIdList><ArticleId IdType="pubmed">9598899</ArticleId></ArticleIdList></Reference><Reference><Citation>Rico MC, Castaneda JL, Manns JM, Uknis AB, Sainz IM, Safadi FF, Popoff SN, Dela Cadena RA. Amelioration of inflammation, angiogenesis and CTGF expression ina n arthritis model by a TSP-1-derived peptide treatment. J Cell Physiol. 2007;211:504&#x2013;512.</Citation><ArticleIdList><ArticleId IdType="pubmed">17219411</ArticleId></ArticleIdList></Reference><Reference><Citation>Park YW, Kang YM, Butterfield J, Detmar M, Goronzy JJ, Weyand CM. Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in rheumatoid arthritis. Am J Pathol. 2004;165:2087&#x2013;2098.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1618704</ArticleId><ArticleId IdType="pubmed">15579451</ArticleId></ArticleIdList></Reference><Reference><Citation>Ingber D, Fujita T, Kishimoto S, Sudo K, Kanamaru T, Brem H, Folkman J. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature. 1990;348:555&#x2013;557.</Citation><ArticleIdList><ArticleId IdType="pubmed">1701033</ArticleId></ArticleIdList></Reference><Reference><Citation>Peacock DJ, Banquerigo ML, Brahn E. Angiogenesis inhibition suppresses collagen arthritis. J Exp Med. 1992;175:1135&#x2013;1138.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2119184</ArticleId><ArticleId IdType="pubmed">1372645</ArticleId></ArticleIdList></Reference><Reference><Citation>Hannig G, Bernier SG, Hoyt JG, Doyle B, Clark E, Karp RM, Lorusso J, Westlin WF. Suppression of inflammation and structural damage in experimental arthritis through molecular targeted therapy with PPI-2458. Arthritis Rheum. 2007;56:850&#x2013;860.</Citation><ArticleIdList><ArticleId IdType="pubmed">17328059</ArticleId></ArticleIdList></Reference><Reference><Citation>O'Dell JR, Blakely KW, Mallek JA, Eckhoff PJ, Leff RD, Wees SJ, Sems KM, Fernandez AM, Palmer WR, Klassen LW, Paulsen GA, Haire CE, Moore GF. Treatment of early seropositive rheumatoid arthritis: A two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum. 2001;44:2235&#x2013;2241.</Citation><ArticleIdList><ArticleId IdType="pubmed">11665963</ArticleId></ArticleIdList></Reference><Reference><Citation>Stone M, Fortin PR, Pacheco-Tena C, Inman RD. Should tetracycline treatment be used more extensively for rheumatoid arthritis? J Rheumatol. 2003;30:2112&#x2013;2122.</Citation><ArticleIdList><ArticleId IdType="pubmed">14528503</ArticleId></ArticleIdList></Reference><Reference><Citation>Ogrendik M. Effects of clarithromycin in patients with active rheumatoid arthritis. Curr Med Res Opin. 2007;23:515&#x2013;522.</Citation><ArticleIdList><ArticleId IdType="pubmed">17355733</ArticleId></ArticleIdList></Reference><Reference><Citation>Nemoto K, Mae T, Abe F, Takeuchi T. Successful treatment with a novel immunosuppressive agent, deoxyspergualin, in type II collagen-induced arthritis in mice. Ann NY Acad Sci. 1993;685:148&#x2013;154.</Citation><ArticleIdList><ArticleId IdType="pubmed">8363219</ArticleId></ArticleIdList></Reference><Reference><Citation>Bernier SG, Lazarus DD, Clark E, Doyle B, Labenski MT, Thompson CD, Westlin WF, Hannig G. A methionine aminopeptidase-2 inhibitor, PPI-2458, for the treatment of rheumatoid arthritis. Proc Natl Acad Sci USA. 2004;101:10768&#x2013;10773.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC490009</ArticleId><ArticleId IdType="pubmed">15249666</ArticleId></ArticleIdList></Reference><Reference><Citation>Yin G, Liu W, An P, Li P, Ding I, Planelles V, Schwarz EM, Min W. Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis. Mol Ther. 2002;5:547&#x2013;554.</Citation><ArticleIdList><ArticleId IdType="pubmed">11991745</ArticleId></ArticleIdList></Reference><Reference><Citation>Takahashi H, Kato K, Miyake K, Hirai Y, Yoshino S, Shimada T. Adeno-associated virus vector-mediated anti-angiogenic gene therapy for collagen-induced arthritis in mice. Clin Exp Rheumatol. 2005;23:455&#x2013;461.</Citation><ArticleIdList><ArticleId IdType="pubmed">16095112</ArticleId></ArticleIdList></Reference><Reference><Citation>Yue L, Shen YX, Feng LJ, Chen FH, Yao HW, Liu LH, Wu Q, Wang H. Blockage of the formation of new blood vessels by recombinant human endostatin contributes to the regression of rat adjuvant arthritis. Eur J Pharmacol. 2007;567:166&#x2013;170.</Citation><ArticleIdList><ArticleId IdType="pubmed">17490637</ArticleId></ArticleIdList></Reference><Reference><Citation>Huang XY, Chen FH, Li J, Xia LJ, Liu YJ, Zhang XM, Yuan FL. Mechanism of fibroblast-like synoviocyte apoptosis induced by recombinant human endostatin in rats with adjuvant arthritis. Anat Rec (Hoboken) 2008;291:1029&#x2013;1037.</Citation><ArticleIdList><ArticleId IdType="pubmed">18509875</ArticleId></ArticleIdList></Reference><Reference><Citation>Kurosaka D, Yoshida K, Yasuda J, Yasuda C, Noda K, Furuya K, Ukichi T, Kingetsu I, Joh K, Yamaguchi N, Saito S, Yamada A. The effect of endostatin evaluated in an experimental animal model of collagen-induced arthritis. Scand J Rheumatol. 2007;36:434&#x2013;441.</Citation><ArticleIdList><ArticleId IdType="pubmed">18092264</ArticleId></ArticleIdList></Reference><Reference><Citation>Kurosaka D, Yasuda J, Yoshida K, Yasuda C, Toyokawa Y, Yokoyama T, Kingetsu I, Yamada A. Kinetics of circulating endothelial progenitor cells in mice with type II collagen arthritis. Blood Cells Mol Dis. 2005;35:236&#x2013;240.</Citation><ArticleIdList><ArticleId IdType="pubmed">16023391</ArticleId></ArticleIdList></Reference><Reference><Citation>Sumariwalla PF, Cao Y, Wu HL, Feldmann EM, Paleolog E. The angiogenesis inhibitor protease-activated kringles 1-5 reduces the severity of murine collagen-induced arthritis. Arthritis Res Ther. 2003;5:R32&#x2013;R39.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC154428</ArticleId><ArticleId IdType="pubmed">12716451</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang CR, Chen SY, Shiau AL, Wu CL, Jou IM, Chao L, Chao J. Upregulation of kallistatin expression in rheumatoid joints. J Rheumatol. 2007;34:2171&#x2013;2176.</Citation><ArticleIdList><ArticleId IdType="pubmed">17937475</ArticleId></ArticleIdList></Reference><Reference><Citation>Mundel TM, Kalluri R. Type IV collagen-derived angiogenesis inhibitors. Microvasc Res. 2007;74:85&#x2013;89.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3998721</ArticleId><ArticleId IdType="pubmed">17602710</ArticleId></ArticleIdList></Reference><Reference><Citation>Mabjeesh NJ, Escuin D, LaVallee TM, Pribluda VS, Swartz GM, Johnson MS, Willard MT, Zhong H, Simons JW, Giannakakou P. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell. 2003;3:363&#x2013;375.</Citation><ArticleIdList><ArticleId IdType="pubmed">12726862</ArticleId></ArticleIdList></Reference><Reference><Citation>Brahn E, Banquerigo ML, Lee JK, Park EJ, Fogler WE, Plum SM. An angiogenesis inhibitor, 2-methoxyestradiol involutes rat collagen-induced arthritis and suppresses gene expression of synovial vascular endothelial growth factor and basic fibroblast growth factor. J Rheumatol. 2008;35:2119&#x2013;2128.</Citation><ArticleIdList><ArticleId IdType="pubmed">18792999</ArticleId></ArticleIdList></Reference><Reference><Citation>Issekutz AC, Sapru K. Modulation of adjuvant arthritis in the rat by 2-methoxyestradiol: An effect independent of an anti-angiogenic action. Int Immunopharmacol. 2008;8:708&#x2013;716.</Citation><ArticleIdList><ArticleId IdType="pubmed">18387513</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">19482623</PMID><DateCompleted><Year>2010</Year><Month>06</Month><Day>16</Day></DateCompleted><DateRevised><Year>2024</Year><Month>03</Month><Day>12</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1945-0508</ISSN><JournalIssue CitedMedium="Internet"><Volume>1</Volume><Issue>1</Issue><PubDate><Year>2009</Year><Month>Jun</Month><Day>01</Day></PubDate></JournalIssue><Title>Frontiers in bioscience (Elite edition)</Title><ISOAbbreviation>Front Biosci (Elite Ed)</ISOAbbreviation></Journal><ArticleTitle>Chemokines and angiogenesis in rheumatoid arthritis.</ArticleTitle><Pagination><StartPage>44</StartPage><EndPage>51</EndPage><MedlinePgn>44-51</MedlinePgn></Pagination><Abstract><AbstractText>In rheumatoid arthritis, chemokines mediate the migration of inflammatory leukocytes into the synovium. Among the four known chemokine families, CXC, CC chemokines and fractalkine seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important during the perpetuation of inflammation underlying rheumatoid arthritis. In this review, authors discuss the role of the most important chemokines and chemokine receptors in arthritis-associated neovascularization. The process and regulation of angiogenesis are described in this context as well. Apart from discussing the pathogenic role of chemokines and chemokine receptors in arthritic vessel formation, authors also review the important relevance of chemokines and angiogenesis for therapeutic intervention.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zoltan</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Division of Rheumatology, Third Department of Medicine, University of Debrecen Medical and Health Sciences Center, Debrecen, H-4004, Hungary. szekanecz@iiibel.dote.hu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pakozdi</LastName><ForeName>Angela</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Szentpetery</LastName><ForeName>Agnes</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Koch</LastName><ForeName>Alisa E</ForeName><Initials>AE</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI040987-08</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI040987</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI-40987</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AR-048267</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AR048267-05</GrantID><Acronym>AR</Acronym><Agency>NIAMS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2009</Year><Month>06</Month><Day>01</Day></ArticleDate></Article><MedlineJournalInfo><Country>Singapore</Country><MedlineTA>Front Biosci (Elite Ed)</MedlineTA><NlmUniqueID>101485240</NlmUniqueID><ISSNLinking>1945-0494</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018925">Chemokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019707">Receptors, Chemokine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018925" MajorTopicYN="N">Chemokines</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009389" MajorTopicYN="N">Neovascularization, Pathologic</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019707" MajorTopicYN="N">Receptors, Chemokine</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013583" MajorTopicYN="N">Synovial Membrane</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2009</Year><Month>6</Month><Day>2</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2009</Year><Month>6</Month><Day>2</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>6</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2010</Year><Month>6</Month><Day>14</Day></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">19482623</ArticleId><ArticleId IdType="mid">NIHMS206813</ArticleId><ArticleId IdType="pmc">PMC2884394</ArticleId><ArticleId IdType="doi">10.2741/E5</ArticleId><ArticleId IdType="pii">5</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Koch AE. Angiogenesis: implications for rheumatoid arthritis. Arthritis Rheum. 1998;41:951&#x2013;962.</Citation><ArticleIdList><ArticleId IdType="pubmed">9627005</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Gaspar L, Koch AE. Angiogenesis in rheumatoid arthritis. Front Biosci. 2005;10:1739&#x2013;1753.</Citation><ArticleIdList><ArticleId IdType="pubmed">15769663</ArticleId></ArticleIdList></Reference><Reference><Citation>Walsh DA. Angiogenesis and arthritis. Rheumatology (Oxford) 1999;38:103&#x2013;112.</Citation><ArticleIdList><ArticleId IdType="pubmed">10342621</ArticleId></ArticleIdList></Reference><Reference><Citation>Paleolog EM, Fava RA. Angiogenesis in rheumatoid arthritis: implications for future therapeutic strategies. Springer Semin Immunopathol. 1998;20:73&#x2013;94.</Citation><ArticleIdList><ArticleId IdType="pubmed">9836370</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Chemokines and angiogenesis. Curr Opin Rheumatol. 2001;13:202&#x2013;208.</Citation><ArticleIdList><ArticleId IdType="pubmed">11333349</ArticleId></ArticleIdList></Reference><Reference><Citation>Rudolph EH, Woods JM. Chemokine expression and regulation of angiogenesis in rheumatoid arthritis. Curr Pharm Des. 2005;11:613&#x2013;631.</Citation><ArticleIdList><ArticleId IdType="pubmed">15720278</ArticleId></ArticleIdList></Reference><Reference><Citation>Auerbach W, Auerbach R. Angiogenesis inhibition. a review. Pharmacol Ther. 1994;63:265&#x2013;311.</Citation><ArticleIdList><ArticleId IdType="pubmed">7530374</ArticleId></ArticleIdList></Reference><Reference><Citation>Freedman SB, Isner JM. Therapeutic angiogenesis for ischemic cardiovascular disease. J Mol Cell Cardiol. 2001;33:379&#x2013;393.</Citation><ArticleIdList><ArticleId IdType="pubmed">11181008</ArticleId></ArticleIdList></Reference><Reference><Citation>Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, William M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S. Expression of VEGFR-2 and AC133 by circulating human CD34 (+) cells identifies a population of functional endothelial precursors. Blood. 2000;95:952&#x2013;958.</Citation><ArticleIdList><ArticleId IdType="pubmed">10648408</ArticleId></ArticleIdList></Reference><Reference><Citation>Grisar J, Aletaha D, Steiner CW, Kapral T, Steiner S, Seidinger D, Weigel G, Schwarzinger I, Wolozcszuk W, Steiner G, Smolen JS. Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation. 2005;111:204&#x2013;211.</Citation><ArticleIdList><ArticleId IdType="pubmed">15642766</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Sz&#xfc;cs G, Szanto S, Koch AE. Chemokines in rheumatic diseases. Curr Drug Targ. 2006;7:91&#x2013;102.</Citation><ArticleIdList><ArticleId IdType="pubmed">16454702</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Koch AE. Macrophages and their products in rheumatoid arthritis. Curr Opin Rheumatol. 2007;19:289&#x2013;295.</Citation><ArticleIdList><ArticleId IdType="pubmed">17414958</ArticleId></ArticleIdList></Reference><Reference><Citation>Imhof BA, Aurrand-Lions M. Adhesion mechanisms regulating the migration of monocytes. Nat Rev Immunol. 2004;4:432&#x2013;444.</Citation><ArticleIdList><ArticleId IdType="pubmed">15173832</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Kim J, Koch AE. Chemokines and chemokine receptors in rheumatoid arthritis. Sem Immunol. 2002;399:1&#x2013;7.</Citation><ArticleIdList><ArticleId IdType="pubmed">12495637</ArticleId></ArticleIdList></Reference><Reference><Citation>Mehrad B, Keane MP, Strieter RM. Chemokines as mediators of angiogenesis. Thromb Haemost. 2007;97:755&#x2013;762.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3353527</ArticleId><ArticleId IdType="pubmed">17479186</ArticleId></ArticleIdList></Reference><Reference><Citation>Koch AE, Polverini PJ, Leibovich SJ. Stimulation of neovascularization by human rheumatoid synovial tissue macrophages. Arthritis Rheum. 1986;29:471&#x2013;479.</Citation><ArticleIdList><ArticleId IdType="pubmed">2423091</ArticleId></ArticleIdList></Reference><Reference><Citation>Buckley CD, Amft N, Bradfield PF, Pilling D, Ross E, Arenzana-Seisdedos F, Amara A, Curnow SJ, Lord RM, Scheel-Toellner D, Salmon M. Persistent induction of the chemokine receptor CXCR4 by TGF-beta 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium. J Immunol. 2000;165:3423&#x2013;3429.</Citation><ArticleIdList><ArticleId IdType="pubmed">10975862</ArticleId></ArticleIdList></Reference><Reference><Citation>Nanki T, Hayashida K, El-Gabalawy HS, Suson S, Shi K, Girschick HJ, Yavuz S, Lipsky PE. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T-cell accumulation in rheumatoid arthritis synovium. J Immunol. 165:6590&#x2013;6598.</Citation><ArticleIdList><ArticleId IdType="pubmed">11086103</ArticleId></ArticleIdList></Reference><Reference><Citation>Manzo A, Paoletti S, Carulli M, Blades MC, Barone F, Yanni G, Fitzgerald O, Bresnihan B, Caporali R, Montecucco C. Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. Eur J Immunol. 2005;35:1347&#x2013;1359.</Citation><ArticleIdList><ArticleId IdType="pubmed">15832291</ArticleId></ArticleIdList></Reference><Reference><Citation>Li T, Zhong J, Chen Y, Qiu X, Zhang T, Ma D, Han W. Expression of chemokine-like factor 1 is upregulated during T lymphocyte activation. Life Sci. 2006;79:519&#x2013;524.</Citation><ArticleIdList><ArticleId IdType="pubmed">16522323</ArticleId></ArticleIdList></Reference><Reference><Citation>Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK, Oppenheim JJ, Murphy WJ. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood. 2000;96:34&#x2013;40.</Citation><ArticleIdList><ArticleId IdType="pubmed">10891427</ArticleId></ArticleIdList></Reference><Reference><Citation>Stamatovic SM, Keep RF, Mostarica-Stojkovic M, Andjelkovic AV. CCL2 regulates angiogenesis via activation of Ets-1 transcription factor. J Immunol. 2006;177:2651&#x2013;2661.</Citation><ArticleIdList><ArticleId IdType="pubmed">16888027</ArticleId></ArticleIdList></Reference><Reference><Citation>Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ. A new class of membrane bound chemokine with a X3C motif. Nature. 1997;385:640&#x2013;644.</Citation><ArticleIdList><ArticleId IdType="pubmed">9024663</ArticleId></ArticleIdList></Reference><Reference><Citation>Ruth JH, Volin MV, Haines GK, III, Koch AE. Fractalkine, a novel chemokine in rheumatoid arthritis and rat adjuvant-induced arthritis. Arthritis Rheum. 2001;44:1568&#x2013;1581.</Citation><ArticleIdList><ArticleId IdType="pubmed">11465708</ArticleId></ArticleIdList></Reference><Reference><Citation>Volin MV, Woods JM, Amin MA, Connors MA, Harlow LA, Koch AE. Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis. Am J Pathol. 2001;159:1521&#x2013;1526.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1850492</ArticleId><ArticleId IdType="pubmed">11583978</ArticleId></ArticleIdList></Reference><Reference><Citation>Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000;12:121&#x2013;127.</Citation><ArticleIdList><ArticleId IdType="pubmed">10714678</ArticleId></ArticleIdList></Reference><Reference><Citation>Walz A, Kunkel SL, Strieter RM. C-X-C chemokines &#x2013; an overview. In: Koch AE, Strieter RM, editors. Chemokines in Disease. Austin: RG Landes Company; 1996. pp. 1&#x2013;25.</Citation></Reference><Reference><Citation>Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, Dzuiba J, Van Damme J, Walz A, Marriott D, Chan SY, Roczniak S, Shanafelt AB. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995;270:27348&#x2013;27357.</Citation><ArticleIdList><ArticleId IdType="pubmed">7592998</ArticleId></ArticleIdList></Reference><Reference><Citation>Castor CW, Andrews PC, Swartz RD, Bignall MC, Aaron BP. The origin, variety, distribution, and biologic fate of connective tissue activating peptide-III isoforms: characteristics in patients with rheumatic, renal, and arterial disease. Arthritis Rheum. 1993;36:1142&#x2013;1153.</Citation><ArticleIdList><ArticleId IdType="pubmed">8343190</ArticleId></ArticleIdList></Reference><Reference><Citation>Caunt M, Hu L, Tang T, Brooks PC, Ibrahim S, Karpatkin S. Growth-regulated oncogene is pivotal in thrombin-induced angiogenesis. Cancer Res. 2006;66:4125&#x2013;4132.</Citation><ArticleIdList><ArticleId IdType="pubmed">16618733</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang D, Wang H, Brown J, Daikoku T, Ning W, Shi Q, Richmond A, Strieter R, Dey SK, DuBois RN. CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J Exp Med. 2006;203:941&#x2013;951.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2118273</ArticleId><ArticleId IdType="pubmed">16567391</ArticleId></ArticleIdList></Reference><Reference><Citation>Boulday G, Haskova Z, Reinders ME, Pal S, Broiscoe DM. Vascular endothelial growth factor-induced signaling pathways in endothelial cells that mediate overexpression of the chemokine IFN-gamma-inducible protein of 10 kDa in vitro andin vivo. J Immunol. 2006;176:3098&#x2013;3107.</Citation><ArticleIdList><ArticleId IdType="pubmed">16493069</ArticleId></ArticleIdList></Reference><Reference><Citation>Bodnar RJ, Yates CC, Wells A. IP-10 blocks vascular endothelial growth factor-induced endothelial cell motility and tube formation via inhibition of calpain. Circ Res. 2006;98:617&#x2013;625.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC3826264</ArticleId><ArticleId IdType="pubmed">16484616</ArticleId></ArticleIdList></Reference><Reference><Citation>Maurer AM, Zhou B, Han ZC. Roles of platelet factor 4 in hematopoiesis and angiogenesis. Growth Factors. 2006;24:242&#x2013;252.</Citation><ArticleIdList><ArticleId IdType="pubmed">17381065</ArticleId></ArticleIdList></Reference><Reference><Citation>Vandercappellen J, Noppen S, Verbeke H, Put W, Conings R, Gouwy M, Schutyser E, Proost P, Sciot R, Geboes K, Opdenakker G, Van Damme J, Struyf S. Stimulation of angiostatic platelet facor-4 variant (CXCL4L1/PF-4var) versus inhibition of angiogenic granulocyte chemotactic protein-2 (CXCL6/GCP-2) in normal and tumoral mesenchymal cells. J Leukoc Biol. 2007 Sep 7; (Epub ahead of print)</Citation><ArticleIdList><ArticleId IdType="pubmed">17827342</ArticleId></ArticleIdList></Reference><Reference><Citation>Struyf S, Burdick MD, Peeters E, van den Broeck K, Dillen C, Proost P, van Damme J, Strieter RM. Platelet factor-4 variant chemokine CXCL4L1 inhibits melanoma and lung carcinoma growth and metastsis by preventing angiogenesis. Cancer Res. 2007;67:5940&#x2013;5948.</Citation><ArticleIdList><ArticleId IdType="pubmed">17575164</ArticleId></ArticleIdList></Reference><Reference><Citation>Pablos JL, Santiago B, Galindo M, Torres C, Brehmer M, Blanco FJ, Garcia-Lazaro FJ. Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. J Immunol. 2003;170:2147&#x2013;2152.</Citation><ArticleIdList><ArticleId IdType="pubmed">12574387</ArticleId></ArticleIdList></Reference><Reference><Citation>Salcedo R, Wasserman K, Young HA, Grimm MC, Howard OM, Anver MR, Kleinman HK, Murphy WJ, Oppenheim JJ. Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1alpha. Am J Pathol. 1999;154:1125&#x2013;1135.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1866563</ArticleId><ArticleId IdType="pubmed">10233851</ArticleId></ArticleIdList></Reference><Reference><Citation>Petit I, Jin D, Rafii S. The SDF-1-CXCR4 signaling pathway. a molecular hub modulating neo-angiogenesis. Trends Immunol. 2007;28:299&#x2013;307.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2952492</ArticleId><ArticleId IdType="pubmed">17560169</ArticleId></ArticleIdList></Reference><Reference><Citation>Liang Z, Brooks J, Willard M, Liang K, Yoon Y, Kang S, Shim H. CXCR4/CXCL12 axis promotes VEGF-mediated tumor angiogenesis through Akt signaling pathway. Biochem Biophys Res Commun. 2007;359:716&#x2013;722.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1986788</ArticleId><ArticleId IdType="pubmed">17559806</ArticleId></ArticleIdList></Reference><Reference><Citation>Deshane J, Chen S, Caballero S, Grochot-Przeczek A, Was H, Li Calzi S, Lach R, Hock TD, Chen B, Hill-Kapturczak N, Siegal GP, Dulak J, Jozkowicz A, Grant MB, Agarwal A. Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1-dependent mechanism. J Exp Med. 2007;204:605&#x2013;618.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1855437</ArticleId><ArticleId IdType="pubmed">17339405</ArticleId></ArticleIdList></Reference><Reference><Citation>Tan Y, Shao H, Eton D, Yang Z, Alonso-Diaz L, Zhang H, Schulick A, Livingstone AS, Yu H. Stromal cell-derived factor-1 enhances pro-angiogenic efft of granulocyte colony stimulating factor. Cardiovasc Res. 2007;73:823&#x2013;832.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2243257</ArticleId><ArticleId IdType="pubmed">17258698</ArticleId></ArticleIdList></Reference><Reference><Citation>Calatozzolo C, Maderna E, Pollo B, Gelati M, Marras C, Silvani A, Croci D, Boiardi A, Salmaggi A. Prognostic value of CXCL12 expression in 40 low-grade oligodendrogliomas and oligoastrocytomas. Cancer Biol Ther. 2006;5:827&#x2013;832.</Citation><ArticleIdList><ArticleId IdType="pubmed">16760646</ArticleId></ArticleIdList></Reference><Reference><Citation>Jin DK, Shido K, Kopp HG, Petit I, Shmelkov SV, Young LM, Hooper AT, Raffii S. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med. 2006;12:557&#x2013;567.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2754288</ArticleId><ArticleId IdType="pubmed">16648859</ArticleId></ArticleIdList></Reference><Reference><Citation>Burns JM, Summers BC, Wang Y, Melikian A, Miao Z, Kuo CJ, Wei K, Wright K, Howard MC, Schall TJ. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion and tumor development. J Exp Med. 2006;203:2201&#x2013;2213.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC2118398</ArticleId><ArticleId IdType="pubmed">16940167</ArticleId></ArticleIdList></Reference><Reference><Citation>Ma J, Wang Q, Fei T, Han JD, Chen YG. MCP-1 mediates TGF-beta-induced angiogenesis by stimulating vascular smooth muscle cell migration. Blood. 2007;109:987&#x2013;994.</Citation><ArticleIdList><ArticleId IdType="pubmed">17032917</ArticleId></ArticleIdList></Reference><Reference><Citation>Fujii T, Yonemitsu Y, Onimaru M, Tanii M, Inoue M, Hasegawa M, Kuwano H, Sueishi K. Nonendothelial mesenchymal cell-derived MCP-1 is required for FGF-2 mediated therapeutic neovascularization. Arterioscler Thromb Vasc Biol. 2006;26:2483&#x2013;2489.</Citation><ArticleIdList><ArticleId IdType="pubmed">16960104</ArticleId></ArticleIdList></Reference><Reference><Citation>Son KN, Hwang J, Kwon BS, Kim J. Human CC chemokine CCL23 enhances expression of matrix metalloproteinase-2 and invasion of vascular endothelial cells. Biochem Biophys Res Commun. 2006;340:498&#x2013;504.</Citation><ArticleIdList><ArticleId IdType="pubmed">16378600</ArticleId></ArticleIdList></Reference><Reference><Citation>Vicari AP, Ait-Yahia S, Chemin K, Mueller A, Zlotnik A, Caux C. Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and immunological mechanisms. J Immunol. 2000;165:1992&#x2013;2000.</Citation><ArticleIdList><ArticleId IdType="pubmed">10925282</ArticleId></ArticleIdList></Reference><Reference><Citation>Lesnik P, Haskell CA, Charo IF. Decreased atherosclerosis in CX3CR1 &#x2212;/&#x2212; mice reveals a role for fractalkine in atherogenesis. J Clin Invest. 2003;111:333&#x2013;340.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC151849</ArticleId><ArticleId IdType="pubmed">12569158</ArticleId></ArticleIdList></Reference><Reference><Citation>McDermott DH, Fong AM, Yang Q. Chemokine receptor mutant CX3CR1-M280 has impaired adhesive function and correlates with protection from cardiovascular disease in humans. J Clin Invest. 2003;111:1241&#x2013;1250.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC152935</ArticleId><ArticleId IdType="pubmed">12697743</ArticleId></ArticleIdList></Reference><Reference><Citation>Borzi RM, Mazzetti I, Cattini L. Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C-C chemokines. Arthritis Rheum. 2000;43:1734&#x2013;1741.</Citation><ArticleIdList><ArticleId IdType="pubmed">10943863</ArticleId></ArticleIdList></Reference><Reference><Citation>Zagzag D, Lukyanov Y, Lan L, Ali MA, Esencay M, Mendez O, Yee H, Voura EB, Newcomb EW. Hypoxia-inducible factor 1 an VEGF upregulate CXCR4 in glioblastoma. implications for angiogenesis and glioma cell invasion. Lab Invest. 2006;86:1221&#x2013;1232.</Citation><ArticleIdList><ArticleId IdType="pubmed">17075581</ArticleId></ArticleIdList></Reference><Reference><Citation>Ochoa O, Sun D, Reyes-Reyna SM, Waite LL, Michalek JE, McManus LM, Shireman PK. Delayed angiogenesis and VEGF production in CCR2&#x2212;/&#x2212; mice during impaired skeletal muscle regeneration. Am J Physiol Regul Integr Comp Physiol. 2007;293:R651&#x2013;R661.</Citation><ArticleIdList><ArticleId IdType="pubmed">17522124</ArticleId></ArticleIdList></Reference><Reference><Citation>Patterson AM, Siddall H, Chamberlain G. Expression of the Duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium. J Pathol. 2002;197:108&#x2013;116.</Citation><ArticleIdList><ArticleId IdType="pubmed">12081195</ArticleId></ArticleIdList></Reference><Reference><Citation>Wang J, Ou ZL, Hou YF, Luo JM, Shen ZZ, Ding J, Shao ZM. Enhanced expression of Duffy antigen receptor for chemokines by breast cancer cells attenuates growth and metastasis potential. Oncogene. 2006;25:7201&#x2013;7211.</Citation><ArticleIdList><ArticleId IdType="pubmed">16785997</ArticleId></ArticleIdList></Reference><Reference><Citation>Amin MA, Mansfield PJ, Pakozdi A, Campbell PL, Ahmed S, Martinez RJ, Koch AE. Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways. Arthritis Rheum. 2007;56:1787&#x2013;1797.</Citation><ArticleIdList><ArticleId IdType="pubmed">17530707</ArticleId></ArticleIdList></Reference><Reference><Citation>McInnes IB. Cytokines. In: Harris ED jr, Budd RC, Firestein GS, Genovese MC, Sergent JS, Ruddy S, Sledge CB, editors. Kelley&#x2019;s Textbook of Rheumatology. 7. Chapter 7. Philadelphia: Elsevier Saunders; 2005. pp. 379&#x2013;389.</Citation></Reference><Reference><Citation>Pakozdi A, Amin MA, Haas CS, Martinez RJ, Haines GK, 3rd, Santos LL, Morand EF, David JR, Koch AE. Macrophage migration inhibitory factor. a mediator of matrix metalloproteinase-2 production in rheumatoid arthritis. Arthritis Res Ther. 2006;8:R132.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1779381</ArticleId><ArticleId IdType="pubmed">16872482</ArticleId></ArticleIdList></Reference><Reference><Citation>Santos LL, Morand EF. The role of macrophage migration inhibitory factor in the inflammatory response and rheumatoid arthritis. Wien Med Wochenschr. 2006;156:11&#x2013;18.</Citation><ArticleIdList><ArticleId IdType="pubmed">16465610</ArticleId></ArticleIdList></Reference><Reference><Citation>Kim HR, Park MK, Cho ML, Yoon CH, Lee SH, Park SH, Leng L, Bucala R, Kang I, Choe J, Kim HY. Macrophage migration inhibitory factor upregulates angiogenic factors and correlates with clinical measures in rheumatoid arthritis. J Rheumatol. 2007;34:927&#x2013;936.</Citation><ArticleIdList><ArticleId IdType="pubmed">17407222</ArticleId></ArticleIdList></Reference><Reference><Citation>Haas CS, Amin MA, Ruth JH, Allen BL, Ahmed S, Pakozdi A, Woods JM, Shahrara S, Koch AE. In vivo inhibition of angiogenesis by interleukin-13 gene therapy in a rat model of rheumatoid arthritis. Arthritis Rheum. 2007;56:2535&#x2013;2548.</Citation><ArticleIdList><ArticleId IdType="pubmed">17665443</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Strieter RM, Koch AE. Cytokines in rheumatoid arthritis. potential targets for pharmacological intervention. Drugs Aging. 1998;12:377&#x2013;390.</Citation><ArticleIdList><ArticleId IdType="pubmed">9606615</ArticleId></ArticleIdList></Reference><Reference><Citation>Szekanecz Z, Haines GK, Lin TR, Harlow LA, Goerdt S, Rayan G, Koch AE. Differential distribution of intercellular adhesion molecules (ICAM-1, ICAM-2 and ICAM-3), and the MS-1 antigen in normal and diseased human synovia. Arthritis Rheum. 1994;37:221&#x2013;231.</Citation><ArticleIdList><ArticleId IdType="pubmed">8129777</ArticleId></ArticleIdList></Reference><Reference><Citation>Loetscher P, Dewald B, Baggiolini M, Seitz M. Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes: effects of anti-rheumatic drugs. Cytokine. 1994;6:162&#x2013;170.</Citation><ArticleIdList><ArticleId IdType="pubmed">8031999</ArticleId></ArticleIdList></Reference><Reference><Citation>Seitz M, Dewald B, Gerber N, Baggiolini M. Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthritis. J Clin Invest. 1991;87:463&#x2013;469.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC295098</ArticleId><ArticleId IdType="pubmed">1899427</ArticleId></ArticleIdList></Reference><Reference><Citation>Lopez-Armada MJ, Sanchez-Pernaute O, Largo R, Diez-Ortego I, Palacios I, Egido J, Herrero-Beaumont G. Modulation of cell recruitment by anti-inflammatory agents in antigen-induced arthritis. Ann Rheum Dis. 2002;61:1027&#x2013;1030.</Citation><ArticleIdList><ArticleId IdType="pmc">PMC1753940</ArticleId><ArticleId IdType="pubmed">12379530</ArticleId></ArticleIdList></Reference><Reference><Citation>Volin MV, Harlow LA, Woods JM, Campbell PL, Amin MA, Tokuhira M, Koch AE. Treatment with sulfasalazine or sulfapyridine, but not 5-aminosalicyclic acid, inhibits basic fibroblast growth factor-induced endothelial cell chemotaxis. Arthritis Rheum. 1999;42:1927&#x2013;1935.</Citation><ArticleIdList><ArticleId IdType="pubmed">10513809</ArticleId></ArticleIdList></Reference><Reference><Citation>Taylor PC, Peters AM, Paleolog E, Chapman PT, Elliott MJ, McCloskey R, Feldmann M, Maini RN. Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis. Arthritis Rheum. 2000;43:38&#x2013;47.</Citation><ArticleIdList><ArticleId IdType="pubmed">10643698</ArticleId></ArticleIdList></Reference><Reference><Citation>Klimiuk PA, Sierakowski S, Domyslawska I, Chwiecko J. Regulation of serum chemokines following infliximab therapy in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2006;24:529&#x2013;533.</Citation><ArticleIdList><ArticleId IdType="pubmed">17181921</ArticleId></ArticleIdList></Reference><Reference><Citation>Zhang R, Tian L, Chen LJ, Hou JM, Li G, Li J, Zhang L, Chen XC, Luo F, Jiang Y, Wei YQ. Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma. Gene Ther. 2006;13:1263&#x2013;1271.</Citation><ArticleIdList><ArticleId IdType="pubmed">16672984</ArticleId></ArticleIdList></Reference><Reference><Citation>Wente MN, Keane MP, Burdick MD, Friess H, Buchler MW, Ceyhan GO, Reber HA, Strieter RM, Hines OJ. Blockade of the chemokine receptor CXCR2 inhibits pancreatic cancer cell-induced angiogenesis. Cancer Lett. 2006;241:221&#x2013;227.</Citation><ArticleIdList><ArticleId IdType="pubmed">16458421</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17893999</PMID><DateCompleted><Year>2007</Year><Month>10</Month><Day>30</Day></DateCompleted><DateRevised><Year>2022</Year><Month>04</Month><Day>08</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0077-8923</ISSN><JournalIssue CitedMedium="Print"><Volume>1108</Volume><PubDate><Year>2007</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Annals of the New York Academy of Sciences</Title><ISOAbbreviation>Ann N Y Acad Sci</ISOAbbreviation></Journal><ArticleTitle>Increased production of the soluble tumor-associated antigens CA19-9, CA125, and CA15-3 in rheumatoid arthritis: potential adhesion molecules in synovial inflammation?</ArticleTitle><Pagination><StartPage>359</StartPage><EndPage>371</EndPage><MedlinePgn>359-71</MedlinePgn></Pagination><Abstract><AbstractText>Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected carcinoembryonic antigen (CEA; CD66) in the rheumatoid (RA) synovium. The production of CEA, CA19-9, CA125, and CA15.3, may be increased in patients with RA, scleroderma, lupus, and Sj&#xf6;gren's syndrome (SS). Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis. We assessed levels of TAAs in the sera of RA patients and healthy subjects. Serum TAA levels were correlated with disease markers including serum rheumatoid factor (RF), C-reactive protein (CRP), and anti-CCP antibody levels, DAS28, age disease duration. TAAs including CEA, CA15-3, CA72-4, CA125, and CA19-9, and neuron-specific enolase (NSE) were assessed by immunoassay in the sera of 75 patients with RA and 50 age- and sex-matched healthy controls. Normal upper limits for these TAAs were 3.4 microg/L, 25 kU/L, 6.9 kU/L, 35 kU/L, 34 kU/L, and 16.3 microg/L, respectively. There were significantly more RA patients showing abnormally high levels of CA125 (10.8% versus 7.1%), CA19-9 (8.1% versus 0%), and CA15-3 (17.6% versus 14.3%) in comparison to controls (P &lt; 0.05). The mean absolute serum levels of CA125 (23.9 +/- 1.8 versus 16.8 +/- 2.2 kU/L) and CA19-9 (14.2 +/- 1.2 versus 10.5 +/- 1.6 kU/L) were also significantly higher in RA compared to controls (P &lt; 0.05). Among RA patients, serum CEA showed significant correlation with RF (r = 0.270; P &lt; 0.05). None of the assessed TAAs showed any correlation with CRP, anti-CCP, DAS28, age or disease duration. The concentration of some TAAs may be elevated in the sera of patients with established RA in comparison to healthy subjects. CEA, CA19-9, CA125, and CA15-3 contain carbohydrate motifs and thus they may be involved in synovitis-associated adhesive events. Furthermore, some TAAs, such as CEA, may also correlate with prognostic factors, such as serum RF levels.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Eva</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Oncology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>S&#xe1;ndor</LastName><ForeName>Zsuzsa</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Antal-Szalm&#xe1;s</LastName><ForeName>P&#xe9;ter</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>So&#xf3;s</LastName><ForeName>Lilla</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Lakos</LastName><ForeName>Gabriella</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Szentp&#xe9;tery</LastName><ForeName>Agnes</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Simkovics</LastName><ForeName>Enik&#xf6;</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Sz&#xe1;nt&#xf3;</LastName><ForeName>J&#xe1;nos</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Kiss</LastName><ForeName>Emese</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Koch</LastName><ForeName>Alisa E</ForeName><Initials>AE</Initials></Author><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Ann N Y Acad Sci</MedlineTA><NlmUniqueID>7506858</NlmUniqueID><ISSNLinking>0077-8923</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001323">Autoantibodies</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018394">CA-125 Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018395">CA-19-9 Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015815">Cell Adhesion Molecules</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018396">Mucin-1</NameOfSubstance></Chemical><Chemical><RegistryNumber>9007-41-4</RegistryNumber><NameOfSubstance UI="D002097">C-Reactive Protein</NameOfSubstance></Chemical><Chemical><RegistryNumber>9009-79-4</RegistryNumber><NameOfSubstance UI="D012217">Rheumatoid Factor</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001323" MajorTopicYN="N">Autoantibodies</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002097" MajorTopicYN="N">C-Reactive Protein</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018394" MajorTopicYN="N">CA-125 Antigen</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018395" MajorTopicYN="N">CA-19-9 Antigen</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015815" MajorTopicYN="N">Cell Adhesion Molecules</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004797" MajorTopicYN="N">Enzyme-Linked Immunosorbent Assay</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018396" MajorTopicYN="N">Mucin-1</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="Y">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012217" MajorTopicYN="N">Rheumatoid Factor</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013585" MajorTopicYN="N">Synovitis</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2007</Year><Month>9</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>10</Month><Day>31</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2007</Year><Month>9</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17893999</ArticleId><ArticleId IdType="doi">10.1196/annals.1422.037</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17893998</PMID><DateCompleted><Year>2007</Year><Month>10</Month><Day>30</Day></DateCompleted><DateRevised><Year>2019</Year><Month>06</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0077-8923</ISSN><JournalIssue CitedMedium="Print"><Volume>1108</Volume><PubDate><Year>2007</Year><Month>Jun</Month></PubDate></JournalIssue><Title>Annals of the New York Academy of Sciences</Title><ISOAbbreviation>Ann N Y Acad Sci</ISOAbbreviation></Journal><ArticleTitle>Accelerated atherosclerosis in rheumatoid arthritis.</ArticleTitle><Pagination><StartPage>349</StartPage><EndPage>358</EndPage><MedlinePgn>349-58</MedlinePgn></Pagination><Abstract><AbstractText>Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. Both traditional, Framingham risk factors and inflammation-associated factors are involved in RA-associated atherosclerosis. Among imaging techniques, the early determination of common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and nitroglycerine-mediated vasodilation (NMD) may be useful to determine atherosclerosis and endothelial dysfunction. We and others found increased ccIMT and impaired FMD in RA patients. Among immunological and metabolic laboratory markers, anticyclic citrullinated peptide (anti-CCP) antibodies, IgM rheumatoid factor, circulating immune complexes, pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), Th0/Th1 T cells, homocysteine, dyslipidemia, decreased folate and vitamin B12 production, and impaired paraoxonase activity may all be involved in the development of vascular disease in RA. The early diagnosis of endothelial dysfunction and atherosclerosis, active immunosuppressive treatment, the use of drugs that control atherosclerosis, changes in sedentary lifestyle, and the close follow-up of RA patients may help to minimize cardiovascular risk in these individuals.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Szekanecz</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Division of Rheumatology, Third Department of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary. szekanecz@iiibel.dote.hu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kerekes</LastName><ForeName>Gy&#xf6;rgy</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>D&#xe9;r</LastName><ForeName>Henriett</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>S&#xe1;ndor</LastName><ForeName>Zsuzsa</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Szab&#xf3;</LastName><ForeName>Zolt&#xe1;n</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>V&#xe9;gv&#xe1;ri</LastName><ForeName>Anik&#xf3;</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Simkovics</LastName><ForeName>Enik&#xf6;</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>So&#xf3;s</LastName><ForeName>Lilla</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Szentp&#xe9;tery</LastName><ForeName>Agnes</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Besenyei</LastName><ForeName>Timea</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Sz&#xfc;cs</LastName><ForeName>Gabriella</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Sz&#xe1;nt&#xf3;</LastName><ForeName>S&#xe1;ndor</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Tam&#xe1;si</LastName><ForeName>L&#xe1;szl&#xf3;</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Szegedi</LastName><ForeName>Gyula</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Shoenfeld</LastName><ForeName>Yehuda</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Solt&#xe9;sz</LastName><ForeName>P&#xe1;l</ForeName><Initials>P</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Ann N Y Acad Sci</MedlineTA><NlmUniqueID>7506858</NlmUniqueID><ISSNLinking>0077-8923</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001172" MajorTopicYN="N">Arthritis, Rheumatoid</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050197" MajorTopicYN="N">Atherosclerosis</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002318" MajorTopicYN="N">Cardiovascular Diseases</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004730" MajorTopicYN="N">Endothelium, Vascular</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012307" MajorTopicYN="N">Risk Factors</DescriptorName></MeshHeading></MeshHeadingList><NumberOfReferences>46</NumberOfReferences></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2007</Year><Month>9</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2007</Year><Month>10</Month><Day>31</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2007</Year><Month>9</Month><Day>26</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17893998</ArticleId><ArticleId IdType="doi">10.1196/annals.1422.036</ArticleId></ArticleIdList></PubmedData></PubmedArticle></PubmedArticleSet>trying2...<BR>

<!DOCTYPE html>
  <html dir="ltr" lang="en">
  <head>
    <!-- Google tag (gtag.js) -->
    <script async src="https://www.googletagmanager.com/gtag/js?id=G-442WFVFXCC"></script>
    <script>
      window.dataLayer = window.dataLayer || [];
      function gtag(){dataLayer.push(arguments);}
      gtag('js', new Date());
    
      gtag('config', 'G-442WFVFXCC');
    </script>
  <meta charset="utf-8">
  <meta http-equiv="X-UA-Compatible" content="IE=edge"><script type="text/javascript">(window.NREUM||(NREUM={})).init={privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]},distributed_tracing:{enabled:true}};(window.NREUM||(NREUM={})).loader_config={agentID:"601503912",accountID:"4767844",trustKey:"4767844",xpid:"UAEBVl5XDBAFXFhUBAEPVFI=",licenseKey:"NRJS-750ae8097b9f1344f1a",applicationID:"589630826"};;/*! For license information please see nr-loader-spa-1.277.0.min.js.LICENSE.txt */
(()=>{var e,t,r={8122:(e,t,r)=>{"use strict";r.d(t,{a:()=>i});var n=r(944);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.R)(3);if(!t||"object"!=typeof t)return(0,n.R)(4);const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{if(null===e[a]){r[a]=null;continue}Array.isArray(e[a])&&Array.isArray(t[a])?r[a]=Array.from(new Set([...e[a],...t[a]])):"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.R)(1,e)}return r}catch(e){(0,n.R)(2,e)}}},2555:(e,t,r)=>{"use strict";r.d(t,{Vp:()=>c,fn:()=>s,x1:()=>u});var n=r(384),i=r(8122);const o={beacon:n.NT.beacon,errorBeacon:n.NT.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){try{const t=c(e);return!!t.licenseKey&&!!t.errorBeacon&&!!t.applicationID}catch(e){return!1}}function c(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function u(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.a)(t,o);const r=(0,n.nY)(e);r&&(r.info=a[e])}},9417:(e,t,r)=>{"use strict";r.d(t,{D0:()=>p,gD:()=>m,xN:()=>g});var n=r(3333),i=r(993);const o=e=>{if(!e||"string"!=typeof e)return!1;try{document.createDocumentFragment().querySelector(e)}catch{return!1}return!0};var a=r(2614),s=r(944),c=r(384),u=r(8122);const d="[data-nr-mask]",l=()=>{const e={feature_flags:[],experimental:{marks:!1,measures:!1,resources:!1},mask_selector:"*",block_selector:"[data-nr-block]",mask_input_options:{color:!1,date:!1,"datetime-local":!1,email:!1,month:!1,number:!1,range:!1,search:!1,tel:!1,text:!1,time:!1,url:!1,week:!1,textarea:!1,select:!1,password:!0}};return{ajax:{deny_list:void 0,block_internal:!0,enabled:!0,harvestTimeSeconds:10,autoStart:!0},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},get feature_flags(){return e.feature_flags},set feature_flags(t){e.feature_flags=t},generic_events:{enabled:!0,harvestTimeSeconds:30,autoStart:!0},harvest:{tooManyRequestsDelay:60},jserrors:{enabled:!0,harvestTimeSeconds:10,autoStart:!0},logging:{enabled:!0,harvestTimeSeconds:10,autoStart:!0,level:i.p_.INFO},metrics:{enabled:!0,autoStart:!0},obfuscate:void 0,page_action:{enabled:!0},page_view_event:{enabled:!0,autoStart:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,autoStart:!0},performance:{get capture_marks(){return e.feature_flags.includes(n.$v.MARKS)||e.experimental.marks},set capture_marks(t){e.experimental.marks=t},get capture_measures(){return e.feature_flags.includes(n.$v.MEASURES)||e.experimental.measures},set capture_measures(t){e.experimental.measures=t},resources:{get enabled(){return e.feature_flags.includes(n.$v.RESOURCES)||e.experimental.resources},set enabled(t){e.experimental.resources=t},asset_types:[],first_party_domains:[],ignore_newrelic:!0}},privacy:{cookies_enabled:!0},proxy:{assets:void 0,beacon:void 0},session:{expiresMs:a.wk,inactiveMs:a.BB},session_replay:{autoStart:!0,enabled:!1,harvestTimeSeconds:60,preload:!1,sampling_rate:10,error_sampling_rate:100,collect_fonts:!1,inline_images:!1,fix_stylesheets:!0,mask_all_inputs:!0,get mask_text_selector(){return e.mask_selector},set mask_text_selector(t){o(t)?e.mask_selector="".concat(t,",").concat(d):""===t||null===t?e.mask_selector=d:(0,s.R)(5,t)},get block_class(){return"nr-block"},get ignore_class(){return"nr-ignore"},get mask_text_class(){return"nr-mask"},get block_selector(){return e.block_selector},set block_selector(t){o(t)?e.block_selector+=",".concat(t):""!==t&&(0,s.R)(6,t)},get mask_input_options(){return e.mask_input_options},set mask_input_options(t){t&&"object"==typeof t?e.mask_input_options={...t,password:!0}:(0,s.R)(7,t)}},session_trace:{enabled:!0,harvestTimeSeconds:10,autoStart:!0},soft_navigations:{enabled:!0,harvestTimeSeconds:10,autoStart:!0},spa:{enabled:!0,harvestTimeSeconds:10,autoStart:!0},ssl:void 0,user_actions:{enabled:!0}}},f={},h="All configuration objects require an agent identifier!";function p(e){if(!e)throw new Error(h);if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function g(e,t){if(!e)throw new Error(h);f[e]=(0,u.a)(t,l());const r=(0,c.nY)(e);r&&(r.init=f[e])}function m(e,t){if(!e)throw new Error(h);var r=p(e);if(r){for(var n=t.split("."),i=0;i<n.length-1;i++)if("object"!=typeof(r=r[n[i]]))return;r=r[n[n.length-1]]}return r}},5603:(e,t,r)=>{"use strict";r.d(t,{a:()=>c,o:()=>s});var n=r(384),i=r(8122);const o={accountID:void 0,trustKey:void 0,agentID:void 0,licenseKey:void 0,applicationID:void 0,xpid:void 0},a={};function s(e){if(!e)throw new Error("All loader-config objects require an agent identifier!");if(!a[e])throw new Error("LoaderConfig for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All loader-config objects require an agent identifier!");a[e]=(0,i.a)(t,o);const r=(0,n.nY)(e);r&&(r.loader_config=a[e])}},3371:(e,t,r)=>{"use strict";r.d(t,{V:()=>f,f:()=>l});var n=r(8122),i=r(384),o=r(6154),a=r(9324);let s=0;const c={buildEnv:a.F3,distMethod:a.Xs,version:a.xv,originTime:o.WN},u={customTransaction:void 0,disabled:!1,isolatedBacklog:!1,loaderType:void 0,maxBytes:3e4,onerror:void 0,ptid:void 0,releaseIds:{},appMetadata:{},session:void 0,denyList:void 0,timeKeeper:void 0,obfuscator:void 0},d={};function l(e){if(!e)throw new Error("All runtime objects require an agent identifier!");if(!d[e])throw new Error("Runtime for ".concat(e," was never set"));return d[e]}function f(e,t){if(!e)throw new Error("All runtime objects require an agent identifier!");d[e]={...(0,n.a)(t,u),...c},Object.hasOwnProperty.call(d[e],"harvestCount")||Object.defineProperty(d[e],"harvestCount",{get:()=>++s});const r=(0,i.nY)(e);r&&(r.runtime=d[e])}},9324:(e,t,r)=>{"use strict";r.d(t,{F3:()=>i,Xs:()=>o,Yq:()=>a,xv:()=>n});const n="1.277.0",i="PROD",o="CDN",a="^2.0.0-alpha.17"},6154:(e,t,r)=>{"use strict";r.d(t,{A4:()=>s,OF:()=>d,RI:()=>i,WN:()=>h,bv:()=>o,gm:()=>a,lR:()=>f,m:()=>u,mw:()=>c,sb:()=>l});var n=r(1863);const i="undefined"!=typeof window&&!!window.document,o="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),a=i?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),s="complete"===a?.document?.readyState,c=Boolean("hidden"===a?.document?.visibilityState),u=""+a?.location,d=/iPad|iPhone|iPod/.test(a.navigator?.userAgent),l=d&&"undefined"==typeof SharedWorker,f=(()=>{const e=a.navigator?.userAgent?.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),h=Date.now()-(0,n.t)()},7295:(e,t,r)=>{"use strict";r.d(t,{Xv:()=>a,gX:()=>i,iW:()=>o});var n=[];function i(e){if(!e||o(e))return!1;if(0===n.length)return!0;for(var t=0;t<n.length;t++){var r=n[t];if("*"===r.hostname)return!1;if(s(r.hostname,e.hostname)&&c(r.pathname,e.pathname))return!1}return!0}function o(e){return void 0===e.hostname}function a(e){if(n=[],e&&e.length)for(var t=0;t<e.length;t++){let r=e[t];if(!r)continue;0===r.indexOf("http://")?r=r.substring(7):0===r.indexOf("https://")&&(r=r.substring(8));const i=r.indexOf("/");let o,a;i>0?(o=r.substring(0,i),a=r.substring(i)):(o=r,a="");let[s]=o.split(":");n.push({hostname:s,pathname:a})}}function s(e,t){return!(e.length>t.length)&&t.indexOf(e)===t.length-e.length}function c(e,t){return 0===e.indexOf("/")&&(e=e.substring(1)),0===t.indexOf("/")&&(t=t.substring(1)),""===e||e===t}},1687:(e,t,r)=>{"use strict";r.d(t,{Ak:()=>c,Ze:()=>l,x3:()=>u});var n=r(7836),i=r(3606),o=r(860),a=r(2646);const s={};function c(e,t){const r={staged:!1,priority:o.P3[t]||0};d(e),s[e].get(t)||s[e].set(t,r)}function u(e,t){e&&s[e]&&(s[e].get(t)&&s[e].delete(t),h(e,t,!1),s[e].size&&f(e))}function d(e){if(!e)throw new Error("agentIdentifier required");s[e]||(s[e]=new Map)}function l(e="",t="feature",r=!1){if(d(e),!e||!s[e].get(t)||r)return h(e,t);s[e].get(t).staged=!0,f(e)}function f(e){const t=Array.from(s[e]);t.every((([e,t])=>t.staged))&&(t.sort(((e,t)=>e[1].priority-t[1].priority)),t.forEach((([t])=>{s[e].delete(t),h(e,t)})))}function h(e,t,r=!0){const o=e?n.ee.get(e):n.ee,s=i.i.handlers;if(!o.aborted&&o.backlog&&s){if(r){const e=o.backlog[t],r=s[t];if(r){for(let t=0;e&&t<e.length;++t)p(e[t],r);Object.entries(r).forEach((([e,t])=>{Object.values(t||{}).forEach((t=>{t[0]?.on&&t[0]?.context()instanceof a.y&&t[0].on(e,t[1])}))}))}}o.isolatedBacklog||delete s[t],o.backlog[t]=null,o.emit("drain-"+t,[])}}function p(e,t){var r=e[1];Object.values(t[r]||{}).forEach((t=>{var r=e[0];if(t[0]===r){var n=t[1],i=e[3],o=e[2];n.apply(i,o)}}))}},7836:(e,t,r)=>{"use strict";r.d(t,{P:()=>c,ee:()=>u});var n=r(384),i=r(8990),o=r(3371),a=r(2646),s=r(5607);const c="nr@context:".concat(s.W),u=function e(t,r){var n={},s={},d={},l=!1;try{l=16===r.length&&(0,o.f)(r).isolatedBacklog}catch(e){}var f={on:p,addEventListener:p,removeEventListener:function(e,t){var r=n[e];if(!r)return;for(var i=0;i<r.length;i++)r[i]===t&&r.splice(i,1)},emit:function(e,r,n,i,o){!1!==o&&(o=!0);if(u.aborted&&!i)return;t&&o&&t.emit(e,r,n);for(var a=h(n),c=g(e),d=c.length,l=0;l<d;l++)c[l].apply(a,r);var p=v()[s[e]];p&&p.push([f,e,r,a]);return a},get:m,listeners:g,context:h,buffer:function(e,t){const r=v();if(t=t||"feature",f.aborted)return;Object.entries(e||{}).forEach((([e,n])=>{s[n]=t,t in r||(r[t]=[])}))},abort:function(){f._aborted=!0,Object.keys(f.backlog).forEach((e=>{delete f.backlog[e]}))},isBuffering:function(e){return!!v()[s[e]]},debugId:r,backlog:l?{}:t&&"object"==typeof t.backlog?t.backlog:{},isolatedBacklog:l};return Object.defineProperty(f,"aborted",{get:()=>{let e=f._aborted||!1;return e||(t&&(e=t.aborted),e)}}),f;function h(e){return e&&e instanceof a.y?e:e?(0,i.I)(e,c,(()=>new a.y(c))):new a.y(c)}function p(e,t){n[e]=g(e).concat(t)}function g(e){return n[e]||[]}function m(t){return d[t]=d[t]||e(f,t)}function v(){return f.backlog}}(void 0,"globalEE"),d=(0,n.Zm)();d.ee||(d.ee=u)},2646:(e,t,r)=>{"use strict";r.d(t,{y:()=>n});class n{constructor(e){this.contextId=e}}},9908:(e,t,r)=>{"use strict";r.d(t,{d:()=>n,p:()=>i});var n=r(7836).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},3606:(e,t,r)=>{"use strict";r.d(t,{i:()=>o});var n=r(9908);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.d,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.d);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3878:(e,t,r)=>{"use strict";function n(e,t){return{capture:e,passive:!1,signal:t}}function i(e,t,r=!1,i){window.addEventListener(e,t,n(r,i))}function o(e,t,r=!1,i){document.addEventListener(e,t,n(r,i))}r.d(t,{DD:()=>o,jT:()=>n,sp:()=>i})},5607:(e,t,r)=>{"use strict";r.d(t,{W:()=>n});const n=(0,r(9566).bz)()},9566:(e,t,r)=>{"use strict";r.d(t,{LA:()=>s,ZF:()=>c,bz:()=>a,el:()=>u});var n=r(6154);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n.gm?.crypto||n.gm?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(30))),i.split("").map((e=>"x"===e?o(t,r++).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n.gm?.crypto||n.gm?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(e)));const a=[];for(var s=0;s<e;s++)a.push(o(r,i++).toString(16));return a.join("")}function c(){return s(16)}function u(){return s(32)}},2614:(e,t,r)=>{"use strict";r.d(t,{BB:()=>a,H3:()=>n,g:()=>u,iL:()=>c,tS:()=>s,uh:()=>i,wk:()=>o});const n="NRBA",i="SESSION",o=144e5,a=18e5,s={STARTED:"session-started",PAUSE:"session-pause",RESET:"session-reset",RESUME:"session-resume",UPDATE:"session-update"},c={SAME_TAB:"same-tab",CROSS_TAB:"cross-tab"},u={OFF:0,FULL:1,ERROR:2}},1863:(e,t,r)=>{"use strict";function n(){return Math.floor(performance.now())}r.d(t,{t:()=>n})},7485:(e,t,r)=>{"use strict";r.d(t,{D:()=>i});var n=r(6154);function i(e){if(0===(e||"").indexOf("data:"))return{protocol:"data"};try{const t=new URL(e,location.href),r={port:t.port,hostname:t.hostname,pathname:t.pathname,search:t.search,protocol:t.protocol.slice(0,t.protocol.indexOf(":")),sameOrigin:t.protocol===n.gm?.location?.protocol&&t.host===n.gm?.location?.host};return r.port&&""!==r.port||("http:"===t.protocol&&(r.port="80"),"https:"===t.protocol&&(r.port="443")),r.pathname&&""!==r.pathname?r.pathname.startsWith("/")||(r.pathname="/".concat(r.pathname)):r.pathname="/",r}catch(e){return{}}}},944:(e,t,r)=>{"use strict";function n(e,t){"function"==typeof console.debug&&console.debug("New Relic Warning: https://github.com/newrelic/newrelic-browser-agent/blob/main/docs/warning-codes.md#".concat(e),t)}r.d(t,{R:()=>n})},5284:(e,t,r)=>{"use strict";r.d(t,{t:()=>c,B:()=>s});var n=r(7836),i=r(6154);const o="newrelic";const a=new Set,s={};function c(e,t){const r=n.ee.get(t);s[t]??={},e&&"object"==typeof e&&(a.has(t)||(r.emit("rumresp",[e]),s[t]=e,a.add(t),function(e={}){try{i.gm.dispatchEvent(new CustomEvent(o,{detail:e}))}catch(e){}}({loaded:!0})))}},8990:(e,t,r)=>{"use strict";r.d(t,{I:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},6389:(e,t,r)=>{"use strict";function n(e,t=500,r={}){const n=r?.leading||!1;let i;return(...r)=>{n&&void 0===i&&(e.apply(this,r),i=setTimeout((()=>{i=clearTimeout(i)}),t)),n||(clearTimeout(i),i=setTimeout((()=>{e.apply(this,r)}),t))}}function i(e){let t=!1;return(...r)=>{t||(t=!0,e.apply(this,r))}}r.d(t,{J:()=>i,s:()=>n})},3304:(e,t,r)=>{"use strict";r.d(t,{A:()=>o});var n=r(7836);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())??""}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}return""}}},5289:(e,t,r)=>{"use strict";r.d(t,{GG:()=>o,sB:()=>a});var n=r(3878);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.sp)("load",e,t)}function a(e){if(i())return e();(0,n.DD)("DOMContentLoaded",e)}},384:(e,t,r)=>{"use strict";r.d(t,{NT:()=>o,US:()=>d,Zm:()=>a,bQ:()=>c,dV:()=>s,nY:()=>u,pV:()=>l});var n=r(6154),i=r(1863);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return n.gm.NREUM||(n.gm.NREUM={}),void 0===n.gm.newrelic&&(n.gm.newrelic=n.gm.NREUM),n.gm.NREUM}function s(){let e=a();return e.o||(e.o={ST:n.gm.setTimeout,SI:n.gm.setImmediate,CT:n.gm.clearTimeout,XHR:n.gm.XMLHttpRequest,REQ:n.gm.Request,EV:n.gm.Event,PR:n.gm.Promise,MO:n.gm.MutationObserver,FETCH:n.gm.fetch,WS:n.gm.WebSocket}),e}function c(e,t){let r=a();r.initializedAgents??={},t.initializedAt={ms:(0,i.t)(),date:new Date},r.initializedAgents[e]=t}function u(e){let t=a();return t.initializedAgents?.[e]}function d(e,t){a()[e]=t}function l(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},2843:(e,t,r)=>{"use strict";r.d(t,{u:()=>i});var n=r(3878);function i(e,t=!1,r,i){(0,n.DD)("visibilitychange",(function(){if(t)return void("hidden"===document.visibilityState&&e());e(document.visibilityState)}),r,i)}},8139:(e,t,r)=>{"use strict";r.d(t,{u:()=>f});var n=r(7836),i=r(3434),o=r(8990),a=r(6154);const s={},c=a.gm.XMLHttpRequest,u="addEventListener",d="removeEventListener",l="nr@wrapped:".concat(n.P);function f(e){var t=function(e){return(e||n.ee).get("events")}(e);if(s[t.debugId]++)return t;s[t.debugId]=1;var r=(0,i.YM)(t,!0);function f(e){r.inPlace(e,[u,d],"-",p)}function p(e,t){return e[1]}return"getPrototypeOf"in Object&&(a.RI&&h(document,f),c&&h(c.prototype,f),h(a.gm,f)),t.on(u+"-start",(function(e,t){var n=e[1];if(null!==n&&("function"==typeof n||"object"==typeof n)){var i=(0,o.I)(n,l,(function(){var e={object:function(){if("function"!=typeof n.handleEvent)return;return n.handleEvent.apply(n,arguments)},function:n}[typeof n];return e?r(e,"fn-",null,e.name||"anonymous"):n}));this.wrapped=e[1]=i}})),t.on(d+"-start",(function(e){e[1]=this.wrapped||e[1]})),t}function h(e,t,...r){let n=e;for(;"object"==typeof n&&!Object.prototype.hasOwnProperty.call(n,u);)n=Object.getPrototypeOf(n);n&&t(n,...r)}},3434:(e,t,r)=>{"use strict";r.d(t,{Jt:()=>o,YM:()=>c});var n=r(7836),i=r(5607);const o="nr@original:".concat(i.W);var a=Object.prototype.hasOwnProperty,s=!1;function c(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");const a="-"===n.charAt(0);for(let s=0;s<t.length;s++){const c=t[s],u=e[c];d(u)||(e[c]=r(u,a?c+n:n,i,c,o))}},r.flag=o,r;function r(t,r,n,s,c){return d(t)?t:(r||(r=""),nrWrapper[o]=t,function(e,t,r){if(Object.defineProperty&&Object.keys)try{return Object.keys(e).forEach((function(r){Object.defineProperty(t,r,{get:function(){return e[r]},set:function(t){return e[r]=t,t}})})),t}catch(e){u([e],r)}for(var n in e)a.call(e,n)&&(t[n]=e[n])}(t,nrWrapper,e),nrWrapper);function nrWrapper(){var o,a,d,l;try{a=this,o=[...arguments],d="function"==typeof n?n(o,a):n||{}}catch(t){u([t,"",[o,a,s],d],e)}i(r+"start",[o,a,s],d,c);try{return l=t.apply(a,o)}catch(e){throw i(r+"err",[o,a,e],d,c),e}finally{i(r+"end",[o,a,l],d,c)}}}function i(r,n,i,o){if(!s||t){var a=s;s=!0;try{e.emit(r,n,i,t,o)}catch(t){u([t,r,n,i],e)}s=a}}}function u(e,t){t||(t=n.ee);try{t.emit("internal-error",e)}catch(e){}}function d(e){return!(e&&"function"==typeof e&&e.apply&&!e[o])}},9300:(e,t,r)=>{"use strict";r.d(t,{T:()=>n});const n=r(860).K7.ajax},3333:(e,t,r)=>{"use strict";r.d(t,{$v:()=>u,TZ:()=>n,Zp:()=>i,kd:()=>c,mq:()=>s,nf:()=>a,qN:()=>o});const n=r(860).K7.genericEvents,i=["auxclick","click","copy","keydown","paste","scrollend"],o=["focus","blur"],a=4,s=1e3,c=["PageAction","UserAction","BrowserPerformance"],u={MARKS:"experimental.marks",MEASURES:"experimental.measures",RESOURCES:"experimental.resources"}},6774:(e,t,r)=>{"use strict";r.d(t,{T:()=>n});const n=r(860).K7.jserrors},993:(e,t,r)=>{"use strict";r.d(t,{ET:()=>o,TZ:()=>a,p_:()=>i});var n=r(860);const i={ERROR:"ERROR",WARN:"WARN",INFO:"INFO",DEBUG:"DEBUG",TRACE:"TRACE"},o="log",a=n.K7.logging},3785:(e,t,r)=>{"use strict";r.d(t,{R:()=>c,b:()=>u});var n=r(9908),i=r(1863),o=r(860),a=r(3969),s=r(993);function c(e,t,r={},c=s.p_.INFO){(0,n.p)(a.xV,["API/logging/".concat(c.toLowerCase(),"/called")],void 0,o.K7.metrics,e),(0,n.p)(s.ET,[(0,i.t)(),t,r,c],void 0,o.K7.logging,e)}function u(e){return"string"==typeof e&&Object.values(s.p_).some((t=>t===e.toUpperCase().trim()))}},3969:(e,t,r)=>{"use strict";r.d(t,{TZ:()=>n,XG:()=>s,rs:()=>i,xV:()=>a,z_:()=>o});const n=r(860).K7.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},6630:(e,t,r)=>{"use strict";r.d(t,{T:()=>n});const n=r(860).K7.pageViewEvent},782:(e,t,r)=>{"use strict";r.d(t,{T:()=>n});const n=r(860).K7.pageViewTiming},6344:(e,t,r)=>{"use strict";r.d(t,{BB:()=>d,G4:()=>o,Qb:()=>l,TZ:()=>i,Ug:()=>a,_s:()=>s,bc:()=>u,yP:()=>c});var n=r(2614);const i=r(860).K7.sessionReplay,o={RECORD:"recordReplay",PAUSE:"pauseReplay",REPLAY_RUNNING:"replayRunning",ERROR_DURING_REPLAY:"errorDuringReplay"},a=.12,s={DomContentLoaded:0,Load:1,FullSnapshot:2,IncrementalSnapshot:3,Meta:4,Custom:5},c={[n.g.ERROR]:15e3,[n.g.FULL]:3e5,[n.g.OFF]:0},u={RESET:{message:"Session was reset",sm:"Reset"},IMPORT:{message:"Recorder failed to import",sm:"Import"},TOO_MANY:{message:"429: Too Many Requests",sm:"Too-Many"},TOO_BIG:{message:"Payload was too large",sm:"Too-Big"},CROSS_TAB:{message:"Session Entity was set to OFF on another tab",sm:"Cross-Tab"},ENTITLEMENTS:{message:"Session Replay is not allowed and will not be started",sm:"Entitlement"}},d=5e3,l={API:"api"}},5270:(e,t,r)=>{"use strict";r.d(t,{Aw:()=>c,CT:()=>u,SR:()=>s});var n=r(384),i=r(9417),o=r(7767),a=r(6154);function s(e){return!!(0,n.dV)().o.MO&&(0,o.V)(e)&&!0===(0,i.gD)(e,"session_trace.enabled")}function c(e){return!0===(0,i.gD)(e,"session_replay.preload")&&s(e)}function u(e,t){const r=t.correctAbsoluteTimestamp(e);return{originalTimestamp:e,correctedTimestamp:r,timestampDiff:e-r,originTime:a.WN,correctedOriginTime:t.correctedOriginTime,originTimeDiff:Math.floor(a.WN-t.correctedOriginTime)}}},3738:(e,t,r)=>{"use strict";r.d(t,{He:()=>i,Kp:()=>s,Lc:()=>u,Rz:()=>d,TZ:()=>n,bD:()=>o,d3:()=>a,jx:()=>l,uP:()=>c});const n=r(860).K7.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState",l=1e3},3962:(e,t,r)=>{"use strict";r.d(t,{AM:()=>o,O2:()=>c,Qu:()=>u,TZ:()=>s,ih:()=>d,pP:()=>a,tC:()=>i});var n=r(860);const i=["click","keydown","submit","popstate"],o="api",a="initialPageLoad",s=n.K7.softNav,c={INITIAL_PAGE_LOAD:"",ROUTE_CHANGE:1,UNSPECIFIED:2},u={INTERACTION:1,AJAX:2,CUSTOM_END:3,CUSTOM_TRACER:4},d={IP:"in progress",FIN:"finished",CAN:"cancelled"}},7378:(e,t,r)=>{"use strict";r.d(t,{$p:()=>x,BR:()=>b,Kp:()=>R,L3:()=>y,Lc:()=>c,NC:()=>o,SG:()=>d,TZ:()=>i,U6:()=>p,UT:()=>m,d3:()=>w,dT:()=>f,e5:()=>E,gx:()=>v,l9:()=>l,oW:()=>h,op:()=>g,rw:()=>u,tH:()=>A,uP:()=>s,wW:()=>T,xq:()=>a});var n=r(384);const i=r(860).K7.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",l="remaining",f="interaction",h="spaNode",p="jsonpNode",g="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=(0,n.dV)().o.ST,w="-start",R="-end",x="-body",T="cb"+R,E="jsTime",A="fetch"},4234:(e,t,r)=>{"use strict";r.d(t,{W:()=>o});var n=r(7836),i=r(1687);class o{constructor(e,t){this.agentIdentifier=e,this.ee=n.ee.get(e),this.featureName=t,this.blocked=!1}deregisterDrain(){(0,i.x3)(this.agentIdentifier,this.featureName)}}},7767:(e,t,r)=>{"use strict";r.d(t,{V:()=>o});var n=r(9417),i=r(6154);const o=e=>i.RI&&!0===(0,n.gD)(e,"privacy.cookies_enabled")},425:(e,t,r)=>{"use strict";r.d(t,{j:()=>j});var n=r(860),i=r(2555),o=r(3371),a=r(9908),s=r(7836),c=r(1687),u=r(5289),d=r(6154),l=r(944),f=r(3969),h=r(384),p=r(6344);const g=["setErrorHandler","finished","addToTrace","addRelease","recordCustomEvent","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId","setApplicationVersion","start",p.G4.RECORD,p.G4.PAUSE,"log","wrapLogger"],m=["setErrorHandler","finished","addToTrace","addRelease"];var v=r(1863),b=r(2614),y=r(993),w=r(3785),R=r(2646),x=r(3434);const T=new Map;function E(e,t,r,n){if("object"!=typeof t||!t||"string"!=typeof r||!r||"function"!=typeof t[r])return(0,l.R)(29);const i=function(e){return(e||s.ee).get("logger")}(e),o=(0,x.YM)(i),a=new R.y(s.P);a.level=n.level,a.customAttributes=n.customAttributes;const c=t[r]?.[x.Jt]||t[r];return T.set(c,a),o.inPlace(t,[r],"wrap-logger-",(()=>T.get(c))),i}function A(){const e=(0,h.pV)();g.forEach((t=>{e[t]=(...r)=>function(t,...r){let n=[];return Object.values(e.initializedAgents).forEach((e=>{e&&e.api?e.exposed&&e.api[t]&&n.push(e.api[t](...r)):(0,l.R)(38,t)})),n.length>1?n:n[0]}(t,...r)}))}const S={};var N=r(9417),_=r(5603),O=r(5284);const I=e=>{const t=e.startsWith("http");e+="/",r.p=t?e:"https://"+e};let P=!1;function j(e,t={},g,R){let{init:x,info:T,loader_config:j,runtime:C={},exposed:k=!0}=t;C.loaderType=g;const L=(0,h.pV)();T||(x=L.init,T=L.info,j=L.loader_config),(0,N.xN)(e.agentIdentifier,x||{}),(0,_.a)(e.agentIdentifier,j||{}),T.jsAttributes??={},d.bv&&(T.jsAttributes.isWorker=!0),(0,i.x1)(e.agentIdentifier,T);const H=(0,N.D0)(e.agentIdentifier),M=[T.beacon,T.errorBeacon];P||(H.proxy.assets&&(I(H.proxy.assets),M.push(H.proxy.assets)),H.proxy.beacon&&M.push(H.proxy.beacon),A(),(0,h.US)("activatedFeatures",O.B),e.runSoftNavOverSpa&&=!0===H.soft_navigations.enabled&&H.feature_flags.includes("soft_nav")),C.denyList=[...H.ajax.deny_list||[],...H.ajax.block_internal?M:[]],C.ptid=e.agentIdentifier,(0,o.V)(e.agentIdentifier,C),e.ee=s.ee.get(e.agentIdentifier),void 0===e.api&&(e.api=function(e,t,h=!1){t||(0,c.Ak)(e,"api");const g={};var R=s.ee.get(e),x=R.get("tracer");S[e]=b.g.OFF,R.on(p.G4.REPLAY_RUNNING,(t=>{S[e]=t}));var T="api-",A=T+"ixn-";function N(t,r,n,o){const a=(0,i.Vp)(e);return null===r?delete a.jsAttributes[t]:(0,i.x1)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),I(T,n,!0,o||null===r?"session":void 0)(t,r)}function _(){}g.log=function(e,{customAttributes:t={},level:r=y.p_.INFO}={}){(0,a.p)(f.xV,["API/log/called"],void 0,n.K7.metrics,R),(0,w.R)(R,e,t,r)},g.wrapLogger=(e,t,{customAttributes:r={},level:i=y.p_.INFO}={})=>{(0,a.p)(f.xV,["API/wrapLogger/called"],void 0,n.K7.metrics,R),E(R,e,t,{customAttributes:r,level:i})},m.forEach((e=>{g[e]=I(T,e,!0,"api")})),g.addPageAction=I(T,"addPageAction",!0,n.K7.genericEvents),g.recordCustomEvent=I(T,"recordCustomEvent",!0,n.K7.genericEvents),g.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,o.f)(e).customTransaction=(r||"http://custom.transaction")+t,I(T,"setPageViewName",!0)()},g.setCustomAttribute=function(e,t,r=!1){if("string"==typeof e){if(["string","number","boolean"].includes(typeof t)||null===t)return N(e,t,"setCustomAttribute",r);(0,l.R)(40,typeof t)}else(0,l.R)(39,typeof e)},g.setUserId=function(e){if("string"==typeof e||null===e)return N("enduser.id",e,"setUserId",!0);(0,l.R)(41,typeof e)},g.setApplicationVersion=function(e){if("string"==typeof e||null===e)return N("application.version",e,"setApplicationVersion",!1);(0,l.R)(42,typeof e)},g.start=()=>{try{(0,a.p)(f.xV,["API/start/called"],void 0,n.K7.metrics,R),R.emit("manual-start-all")}catch(e){(0,l.R)(23,e)}},g[p.G4.RECORD]=function(){(0,a.p)(f.xV,["API/recordReplay/called"],void 0,n.K7.metrics,R),(0,a.p)(p.G4.RECORD,[],void 0,n.K7.sessionReplay,R)},g[p.G4.PAUSE]=function(){(0,a.p)(f.xV,["API/pauseReplay/called"],void 0,n.K7.metrics,R),(0,a.p)(p.G4.PAUSE,[],void 0,n.K7.sessionReplay,R)},g.interaction=function(e){return(new _).get("object"==typeof e?e:{})};const O=_.prototype={createTracer:function(e,t){var r={},i=this,o="function"==typeof t;return(0,a.p)(f.xV,["API/createTracer/called"],void 0,n.K7.metrics,R),h||(0,a.p)(A+"tracer",[(0,v.t)(),e,r],i,n.K7.spa,R),function(){if(x.emit((o?"":"no-")+"fn-start",[(0,v.t)(),i,o],r),o)try{return t.apply(this,arguments)}catch(e){const t="string"==typeof e?new Error(e):e;throw x.emit("fn-err",[arguments,this,t],r),t}finally{x.emit("fn-end",[(0,v.t)()],r)}}}};function I(e,t,r,i){return function(){return(0,a.p)(f.xV,["API/"+t+"/called"],void 0,n.K7.metrics,R),i&&(0,a.p)(e+t,[r?(0,v.t)():performance.now(),...arguments],r?null:this,i,R),r?void 0:this}}function P(){r.e(478).then(r.bind(r,8778)).then((({setAPI:t})=>{t(e),(0,c.Ze)(e,"api")})).catch((e=>{(0,l.R)(27,e),R.abort()}))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{O[e]=I(A,e,void 0,h?n.K7.softNav:n.K7.spa)})),g.setCurrentRouteName=h?I(A,"routeName",void 0,n.K7.softNav):I(T,"routeName",!0,n.K7.spa),g.noticeError=function(t,r){"string"==typeof t&&(t=new Error(t)),(0,a.p)(f.xV,["API/noticeError/called"],void 0,n.K7.metrics,R),(0,a.p)("err",[t,(0,v.t)(),!1,r,!!S[e]],void 0,n.K7.jserrors,R)},d.RI?(0,u.GG)((()=>P()),!0):P(),g}(e.agentIdentifier,R,e.runSoftNavOverSpa)),void 0===e.exposed&&(e.exposed=k),P=!0}},8374:(e,t,r)=>{r.nc=(()=>{try{return document?.currentScript?.nonce}catch(e){}return""})()},860:(e,t,r)=>{"use strict";r.d(t,{$J:()=>o,K7:()=>n,P3:()=>i});const n={ajax:"ajax",genericEvents:"generic_events",jserrors:"jserrors",logging:"logging",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",softNav:"soft_navigations",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.spa]:5,[n.ajax]:6,[n.sessionTrace]:7,[n.softNav]:8,[n.sessionReplay]:9,[n.logging]:10,[n.genericEvents]:11},o={[n.pageViewTiming]:"events",[n.ajax]:"events",[n.spa]:"events",[n.softNav]:"events",[n.metrics]:"jserrors",[n.jserrors]:"jserrors",[n.sessionTrace]:"browser/blobs",[n.sessionReplay]:"browser/blobs",[n.logging]:"browser/logs",[n.genericEvents]:"ins"}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>({212:"nr-spa-compressor",249:"nr-spa-recorder",478:"nr-spa"}[e]+"-1.277.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA-1.277.0.PROD:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d<u.length;d++){var l=u[d];if(l.getAttribute("src")==r||l.getAttribute("data-webpack")==t+o){s=l;break}}if(!s){c=!0;var f={478:"sha512-AgX6f6qOxyV4l/Fg8saiNsK37oY3qvFRTOkwua+LDBTL7KUv+eoUSnunEaP3OvjJ1ZiSn43xQyjf9TWbqq8FVQ==",249:"sha512-43TwsElpnwfBCx+EERv4zX5fDsbQLB0w+NTEOt/flpNK9wKjMch+SQIUgLVqaF8jJt5qUeNPsDi/Zk+jgt3SLw==",212:"sha512-/Y+2vKPi087MH5FY89Cw9ahyQ2qnbVj7M2MganYRhmEg4Xos9v/cFPZviY2a1m17D9zpXkOtPsycYXk2AV0huA=="};(s=document.createElement("script")).charset="utf-8",s.timeout=120,i.nc&&s.setAttribute("nonce",i.nc),s.setAttribute("data-webpack",t+o),s.src=r,0!==s.src.indexOf(window.location.origin+"/")&&(s.crossOrigin="anonymous"),f[a]&&(s.integrity=f[a])}e[r]=[n];var h=(t,n)=>{s.onerror=s.onload=null,clearTimeout(p);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},p=setTimeout(h.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=h.bind(null,s.onerror),s.onload=h.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.p="https://js-agent.newrelic.com/",(()=>{var e={38:0,788:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u<a.length;u++)o=a[u],i.o(e,o)&&e[o]&&e[o][0](),e[o]=0},r=self["webpackChunk:NRBA-1.277.0.PROD"]=self["webpackChunk:NRBA-1.277.0.PROD"]||[];r.forEach(t.bind(null,0)),r.push=t.bind(null,r.push.bind(r))})(),(()=>{"use strict";i(8374);var e=i(944),t=i(6344),r=i(9566);class n{agentIdentifier;constructor(e=(0,r.LA)(16)){this.agentIdentifier=e}#e(t,...r){if("function"==typeof this.api?.[t])return this.api[t](...r);(0,e.R)(35,t)}addPageAction(e,t){return this.#e("addPageAction",e,t)}recordCustomEvent(e,t){return this.#e("recordCustomEvent",e,t)}setPageViewName(e,t){return this.#e("setPageViewName",e,t)}setCustomAttribute(e,t,r){return this.#e("setCustomAttribute",e,t,r)}noticeError(e,t){return this.#e("noticeError",e,t)}setUserId(e){return this.#e("setUserId",e)}setApplicationVersion(e){return this.#e("setApplicationVersion",e)}setErrorHandler(e){return this.#e("setErrorHandler",e)}addRelease(e,t){return this.#e("addRelease",e,t)}log(e,t){return this.#e("log",e,t)}}class o extends n{#e(t,...r){if("function"==typeof this.api?.[t])return this.api[t](...r);(0,e.R)(35,t)}start(){return this.#e("start")}finished(e){return this.#e("finished",e)}recordReplay(){return this.#e(t.G4.RECORD)}pauseReplay(){return this.#e(t.G4.PAUSE)}addToTrace(e){return this.#e("addToTrace",e)}setCurrentRouteName(e){return this.#e("setCurrentRouteName",e)}interaction(){return this.#e("interaction")}wrapLogger(e,t,r){return this.#e("wrapLogger",e,t,r)}}var a=i(860),s=i(9417);const c=Object.values(a.K7);function u(e){const t={};return c.forEach((r=>{t[r]=function(e,t){return!0===(0,s.gD)(t,"".concat(e,".enabled"))}(r,e)})),t}var d=i(425);var l=i(1687),f=i(4234),h=i(5289),p=i(6154),g=i(5270),m=i(7767),v=i(6389);class b extends f.W{constructor(e,t,r=!0){super(e.agentIdentifier,t),this.auto=r,this.abortHandler=void 0,this.featAggregate=void 0,this.onAggregateImported=void 0,!1===e.init[this.featureName].autoStart&&(this.auto=!1),this.auto?(0,l.Ak)(e.agentIdentifier,t):this.ee.on("manual-start-all",(0,v.J)((()=>{(0,l.Ak)(e.agentIdentifier,this.featureName),this.auto=!0,this.importAggregator(e)})))}importAggregator(t,r={}){if(this.featAggregate||!this.auto)return;let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let o;try{if((0,m.V)(this.agentIdentifier)){const{setupAgentSession:e}=await i.e(478).then(i.bind(i,6526));o=e(t)}}catch(t){(0,e.R)(20,t),this.ee.emit("internal-error",[t]),this.featureName===a.K7.sessionReplay&&this.abortHandler?.()}try{if(t.sharedAggregator)await t.sharedAggregator;else{t.sharedAggregator=i.e(478).then(i.bind(i,9337));const{EventAggregator:e}=await t.sharedAggregator;t.sharedAggregator=new e}if(!this.#t(this.featureName,o))return(0,l.Ze)(this.agentIdentifier,this.featureName),void n(!1);const{lazyFeatureLoader:e}=await i.e(478).then(i.bind(i,6103)),{Aggregate:a}=await e(this.featureName,"aggregate");this.featAggregate=new a(t,r),n(!0)}catch(t){(0,e.R)(34,t),this.abortHandler?.(),(0,l.Ze)(this.agentIdentifier,this.featureName,!0),n(!1),this.ee&&this.ee.abort()}};p.RI?(0,h.GG)((()=>o()),!0):o()}#t(e,t){switch(e){case a.K7.sessionReplay:return(0,g.SR)(this.agentIdentifier)&&!!t;case a.K7.sessionTrace:return!!t;default:return!0}}}var y=i(6630);class w extends b{static featureName=y.T;constructor(e,t=!0){super(e,y.T,t),this.importAggregator(e)}}var R=i(384);var x=i(9908),T=i(2843),E=i(3878),A=i(782),S=i(1863);class N extends b{static featureName=A.T;constructor(e,t=!0){super(e,A.T,t),p.RI&&((0,T.u)((()=>(0,x.p)("docHidden",[(0,S.t)()],void 0,A.T,this.ee)),!0),(0,E.sp)("pagehide",(()=>(0,x.p)("winPagehide",[(0,S.t)()],void 0,A.T,this.ee))),this.importAggregator(e))}}var _=i(3969);class O extends b{static featureName=_.TZ;constructor(e,t=!0){super(e,_.TZ,t),this.importAggregator(e)}}var I=i(6774),P=i(3304);class j{constructor(e,t,r,n,i){this.name="UncaughtError",this.message="string"==typeof e?e:(0,P.A)(e),this.sourceURL=t,this.line=r,this.column=n,this.__newrelic=i}}function C(e){return H(e)?e:new j(void 0!==e?.message?e.message:e,e?.filename||e?.sourceURL,e?.lineno||e?.line,e?.colno||e?.col,e?.__newrelic)}function k(e){const t="Unhandled Promise Rejection";if(!e?.reason)return;if(H(e.reason))try{return e.reason.message=t+": "+e.reason.message,C(e.reason)}catch(t){return C(e.reason)}const r=C(e.reason);return r.message=t+": "+r?.message,r}function L(e){if(e.error instanceof SyntaxError&&!/:\d+$/.test(e.error.stack?.trim())){const t=new j(e.message,e.filename,e.lineno,e.colno,e.error.__newrelic);return t.name=SyntaxError.name,t}return H(e.error)?e.error:C(e)}function H(e){return e instanceof Error&&!!e.stack}class M extends b{static featureName=I.T;#r=!1;constructor(e,r=!0){super(e,I.T,r);try{this.removeOnAbort=new AbortController}catch(e){}this.ee.on("internal-error",((e,t)=>{this.abortHandler&&(0,x.p)("ierr",[C(e),(0,S.t)(),!0,{},this.#r,t],void 0,this.featureName,this.ee)})),this.ee.on(t.G4.REPLAY_RUNNING,(e=>{this.#r=e})),p.gm.addEventListener("unhandledrejection",(e=>{this.abortHandler&&(0,x.p)("err",[k(e),(0,S.t)(),!1,{unhandledPromiseRejection:1},this.#r],void 0,this.featureName,this.ee)}),(0,E.jT)(!1,this.removeOnAbort?.signal)),p.gm.addEventListener("error",(e=>{this.abortHandler&&(0,x.p)("err",[L(e),(0,S.t)(),!1,{},this.#r],void 0,this.featureName,this.ee)}),(0,E.jT)(!1,this.removeOnAbort?.signal)),this.abortHandler=this.#n,this.importAggregator(e)}#n(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}var D=i(8990);let K=1;const U="nr@id";function V(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===p.gm?0:(0,D.I)(e,U,(function(){return K++}))}function G(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,P.A)(e).length}catch(e){return}}}var F=i(8139),B=i(7836),W=i(3434);const z={},q=["open","send"];function Z(t){var r=t||B.ee;const n=function(e){return(e||B.ee).get("xhr")}(r);if(void 0===p.gm.XMLHttpRequest)return n;if(z[n.debugId]++)return n;z[n.debugId]=1,(0,F.u)(r);var i=(0,W.YM)(n),o=p.gm.XMLHttpRequest,a=p.gm.MutationObserver,s=p.gm.Promise,c=p.gm.setInterval,u="readystatechange",d=["onload","onerror","onabort","onloadstart","onloadend","onprogress","ontimeout"],l=[],f=p.gm.XMLHttpRequest=function(t){const r=new o(t),a=n.context(r);try{n.emit("new-xhr",[r],a),r.addEventListener(u,(s=a,function(){var e=this;e.readyState>3&&!s.resolved&&(s.resolved=!0,n.emit("xhr-resolved",[],e)),i.inPlace(e,d,"fn-",y)}),(0,E.jT)(!1))}catch(t){(0,e.R)(15,t);try{n.emit("internal-error",[t])}catch(e){}}var s;return r};function h(e,t){i.inPlace(t,["onreadystatechange"],"fn-",y)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,f),f.prototype=o.prototype,i.inPlace(f.prototype,q,"-xhr-",y),n.on("send-xhr-start",(function(e,t){h(e,t),function(e){l.push(e),a&&(g?g.then(b):c?c(b):(m=-m,v.data=m))}(t)})),n.on("open-xhr-start",h),a){var g=s&&s.resolve();if(!c&&!s){var m=1,v=document.createTextNode(m);new a(b).observe(v,{characterData:!0})}}else r.on("fn-end",(function(e){e[0]&&e[0].type===u||b()}));function b(){for(var e=0;e<l.length;e++)h(0,l[e]);l.length&&(l=[])}function y(e,t){return t}return n}var Y="fetch-",X=Y+"body-",J=["arrayBuffer","blob","json","text","formData"],Q=p.gm.Request,ee=p.gm.Response,te="prototype";const re={};function ne(e){const t=function(e){return(e||B.ee).get("fetch")}(e);if(!(Q&&ee&&p.gm.fetch))return t;if(re[t.debugId]++)return t;function r(e,r,n){var i=e[r];"function"==typeof i&&(e[r]=function(){var e,r=[...arguments],o={};t.emit(n+"before-start",[r],o),o[B.P]&&o[B.P].dt&&(e=o[B.P].dt);var a=i.apply(this,r);return t.emit(n+"start",[r,e],a),a.then((function(e){return t.emit(n+"end",[null,e],a),e}),(function(e){throw t.emit(n+"end",[e],a),e}))})}return re[t.debugId]=1,J.forEach((e=>{r(Q[te],e,X),r(ee[te],e,X)})),r(p.gm,"fetch",Y),t.on(Y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(Y+"done",[null,r],n)}else t.emit(Y+"done",[e],n)})),t}var ie=i(7485),oe=i(5603);class ae{constructor(e){this.agentIdentifier=e}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var t=(0,oe.o)(this.agentIdentifier);if(!t)return null;var n=(t.accountID||"").toString()||null,i=(t.agentID||"").toString()||null,o=(t.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,r.ZF)(),s=(0,r.el)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof p.gm?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,P.A)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var t=!1,r={};if((0,s.gD)(this.agentIdentifier,"distributed_tracing")&&(r=(0,s.D0)(this.agentIdentifier).distributed_tracing),e.sameOrigin)t=!0;else if(r.allowed_origins instanceof Array)for(var n=0;n<r.allowed_origins.length;n++){var i=(0,ie.D)(r.allowed_origins[n]);if(e.hostname===i.hostname&&e.protocol===i.protocol&&e.port===i.port){t=!0;break}}return t}isDtEnabled(){var e=(0,s.gD)(this.agentIdentifier,"distributed_tracing");return!!e&&!!e.enabled}excludeNewrelicHeader(){var e=(0,s.gD)(this.agentIdentifier,"distributed_tracing");return!!e&&!!e.exclude_newrelic_header}useNewrelicHeaderForCors(){var e=(0,s.gD)(this.agentIdentifier,"distributed_tracing");return!!e&&!1!==e.cors_use_newrelic_header}useTraceContextHeadersForCors(){var e=(0,s.gD)(this.agentIdentifier,"distributed_tracing");return!!e&&!!e.cors_use_tracecontext_headers}}var se=i(9300),ce=i(7295),ue=["load","error","abort","timeout"],de=ue.length,le=(0,R.dV)().o.REQ,fe=(0,R.dV)().o.XHR;class he extends b{static featureName=se.T;constructor(e,t=!0){super(e,se.T,t),this.dt=new ae(e.agentIdentifier),this.handler=(e,t,r,n)=>(0,x.p)(e,t,r,n,this.ee);try{const e={xmlhttprequest:"xhr",fetch:"fetch",beacon:"beacon"};p.gm?.performance?.getEntriesByType("resource").forEach((t=>{if(t.initiatorType in e&&0!==t.responseStatus){const r={status:t.responseStatus},n={rxSize:t.transferSize,duration:Math.floor(t.duration),cbTime:0};pe(r,t.name),this.handler("xhr",[r,n,t.startTime,t.responseEnd,e[t.initiatorType]],void 0,a.K7.ajax)}}))}catch(e){}ne(this.ee),Z(this.ee),function(e,t,r,n){function i(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=R,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){T(t,e)}),(0,E.jT)(!1)),p.lR||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,E.jT)(!1))}function o(e){this.params={method:e[0]},pe(this,e[1]),this.metrics={}}function s(t,r){e.loader_config.xpid&&this.sameOrigin&&r.setRequestHeader("X-NewRelic-ID",e.loader_config.xpid);var i=n.generateTracePayload(this.parsedOrigin);if(i){var o=!1;i.newrelicHeader&&(r.setRequestHeader("newrelic",i.newrelicHeader),o=!0),i.traceContextParentHeader&&(r.setRequestHeader("traceparent",i.traceContextParentHeader),i.traceContextStateHeader&&r.setRequestHeader("tracestate",i.traceContextStateHeader),o=!0),o&&(this.dt=i)}}function c(e,r){var n=this.metrics,i=e[0],o=this;if(n&&i){var a=G(i);a&&(n.txSize=a)}this.startTime=(0,S.t)(),this.body=i,this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof r.onload)&&"function"==typeof o.end)&&o.end(r)}catch(e){try{t.emit("internal-error",[e])}catch(e){}}};for(var s=0;s<de;s++)r.addEventListener(ue[s],this.listener,(0,E.jT)(!1))}function u(e,t,r){this.cbTime+=e,t?this.onloadCalled=!0:this.called+=1,this.called!==this.totalCbs||!this.onloadCalled&&"function"==typeof r.onload||"function"!=typeof this.end||this.end(r)}function d(e,t){var r=""+V(e)+!!t;this.xhrGuids&&!this.xhrGuids[r]&&(this.xhrGuids[r]=!0,this.totalCbs+=1)}function l(e,t){var r=""+V(e)+!!t;this.xhrGuids&&this.xhrGuids[r]&&(delete this.xhrGuids[r],this.totalCbs-=1)}function f(){this.endTime=(0,S.t)()}function h(e,r){r instanceof fe&&"load"===e[0]&&t.emit("xhr-load-added",[e[1],e[2]],r)}function g(e,r){r instanceof fe&&"load"===e[0]&&t.emit("xhr-load-removed",[e[1],e[2]],r)}function m(e,t,r){t instanceof fe&&("onload"===r&&(this.onload=!0),("load"===(e[0]&&e[0].type)||this.onload)&&(this.xhrCbStart=(0,S.t)()))}function v(e,r){this.xhrCbStart&&t.emit("xhr-cb-time",[(0,S.t)()-this.xhrCbStart,this.onload,r],r)}function b(e){var t,r=e[1]||{};if("string"==typeof e[0]?0===(t=e[0]).length&&p.RI&&(t=""+p.gm.location.href):e[0]&&e[0].url?t=e[0].url:p.gm?.URL&&e[0]&&e[0]instanceof URL?t=e[0].href:"function"==typeof e[0].toString&&(t=e[0].toString()),"string"==typeof t&&0!==t.length){t&&(this.parsedOrigin=(0,ie.D)(t),this.sameOrigin=this.parsedOrigin.sameOrigin);var i=n.generateTracePayload(this.parsedOrigin);if(i&&(i.newrelicHeader||i.traceContextParentHeader))if(e[0]&&e[0].headers)s(e[0].headers,i)&&(this.dt=i);else{var o={};for(var a in r)o[a]=r[a];o.headers=new Headers(r.headers||{}),s(o.headers,i)&&(this.dt=i),e.length>1?e[1]=o:e.push(o)}}function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function y(e,t){this.params={},this.metrics={},this.startTime=(0,S.t)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof le?r=i.url:p.gm?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),pe(this,r);var o=(""+(i&&i instanceof le&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.body=n.body,this.txSize=G(n.body)||0}function w(e,t){if(this.endTime=(0,S.t)(),this.params||(this.params={}),(0,ce.iW)(this.params))return;let n;this.params.status=t?t.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);const i={txSize:this.txSize,rxSize:n,duration:(0,S.t)()-this.startTime};r("xhr",[this.params,i,this.startTime,this.endTime,"fetch"],this,a.K7.ajax)}function R(e){const t=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(let t=0;t<de;t++)e.removeEventListener(ue[t],this.listener,!1);t.aborted||(0,ce.iW)(t)||(n.duration=(0,S.t)()-this.startTime,this.loadCaptureCalled||4!==e.readyState?null==t.status&&(t.status=0):T(this,e),n.cbTime=this.cbTime,r("xhr",[t,n,this.startTime,this.endTime,"xhr"],this,a.K7.ajax))}}function T(e,r){e.params.status=r.status;var n=function(e,t){var r=e.responseType;return"json"===r&&null!==t?t:"arraybuffer"===r||"blob"===r||"json"===r?G(e.response):"text"===r||""===r||void 0===r?G(e.responseText):void 0}(r,e.lastSize);if(n&&(e.metrics.rxSize=n),e.sameOrigin){var i=r.getResponseHeader("X-NewRelic-App-Data");i&&((0,x.p)(_.rs,["Ajax/CrossApplicationTracing/Header/Seen"],void 0,a.K7.metrics,t),e.params.cat=i.split(", ").pop())}e.loadCaptureCalled=!0}t.on("new-xhr",i),t.on("open-xhr-start",o),t.on("open-xhr-end",s),t.on("send-xhr-start",c),t.on("xhr-cb-time",u),t.on("xhr-load-added",d),t.on("xhr-load-removed",l),t.on("xhr-resolved",f),t.on("addEventListener-end",h),t.on("removeEventListener-end",g),t.on("fn-end",v),t.on("fetch-before-start",b),t.on("fetch-start",y),t.on("fn-start",m),t.on("fetch-done",w)}(e,this.ee,this.handler,this.dt),this.importAggregator(e)}}function pe(e,t){var r=(0,ie.D)(t),n=e.params||e;n.hostname=r.hostname,n.port=r.port,n.protocol=r.protocol,n.host=r.hostname+":"+r.port,n.pathname=r.pathname,e.parsedOrigin=r,e.sameOrigin=r.sameOrigin}const ge={},me=["pushState","replaceState"];function ve(e){const t=function(e){return(e||B.ee).get("history")}(e);return!p.RI||ge[t.debugId]++||(ge[t.debugId]=1,(0,W.YM)(t).inPlace(window.history,me,"-")),t}var be=i(3738);const{He:ye,bD:we,d3:Re,Kp:xe,TZ:Te,Lc:Ee,uP:Ae,Rz:Se}=be;class Ne extends b{static featureName=Te;constructor(e,t=!0){super(e,Te,t);if(!(0,m.V)(this.agentIdentifier))return void this.deregisterDrain();const r=this.ee;let n;ve(r),this.eventsEE=(0,F.u)(r),this.eventsEE.on(Ae,(function(e,t){this.bstStart=(0,S.t)()})),this.eventsEE.on(Ee,(function(e,t){(0,x.p)("bst",[e[0],t,this.bstStart,(0,S.t)()],void 0,a.K7.sessionTrace,r)})),r.on(Se+Re,(function(e){this.time=(0,S.t)(),this.startPath=location.pathname+location.hash})),r.on(Se+xe,(function(e){(0,x.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,a.K7.sessionTrace,r)}));try{n=new PerformanceObserver((e=>{const t=e.getEntries();(0,x.p)(ye,[t],void 0,a.K7.sessionTrace,r)})),n.observe({type:we,buffered:!0})}catch(e){}this.importAggregator(e,{resourceObserver:n})}}var _e=i(2614);class Oe extends b{static featureName=t.TZ;#i;#o;constructor(e,r=!0){let n;super(e,t.TZ,r),this.replayRunning=!1,this.#o=e;try{n=JSON.parse(localStorage.getItem("".concat(_e.H3,"_").concat(_e.uh)))}catch(e){}(0,g.SR)(e.agentIdentifier)&&this.ee.on(t.G4.RECORD,(()=>this.#a())),this.#s(n)?(this.#i=n?.sessionReplayMode,this.#c()):this.importAggregator(e),this.ee.on("err",(e=>{this.replayRunning&&(this.errorNoticed=!0,(0,x.p)(t.G4.ERROR_DURING_REPLAY,[e],void 0,this.featureName,this.ee))})),this.ee.on(t.G4.REPLAY_RUNNING,(e=>{this.replayRunning=e}))}#s(e){return e&&(e.sessionReplayMode===_e.g.FULL||e.sessionReplayMode===_e.g.ERROR)||(0,g.Aw)(this.agentIdentifier)}#u=!1;async#c(e){if(!this.#u){this.#u=!0;try{const{Recorder:t}=await Promise.all([i.e(478),i.e(249)]).then(i.bind(i,8589));this.recorder??=new t({mode:this.#i,agentIdentifier:this.agentIdentifier,trigger:e,ee:this.ee}),this.recorder.startRecording(),this.abortHandler=this.recorder.stopRecording}catch(e){}this.importAggregator(this.#o,{recorder:this.recorder,errorNoticed:this.errorNoticed})}}#a(){this.featAggregate?this.featAggregate.mode!==_e.g.FULL&&this.featAggregate.initializeRecording(_e.g.FULL,!0):(this.#i=_e.g.FULL,this.#c(t.Qb.API),this.recorder&&this.recorder.parent.mode!==_e.g.FULL&&(this.recorder.parent.mode=_e.g.FULL,this.recorder.stopRecording(),this.recorder.startRecording(),this.abortHandler=this.recorder.stopRecording))}}var Ie=i(3962);class Pe extends b{static featureName=Ie.TZ;constructor(e,t=!0){if(super(e,Ie.TZ,t),!p.RI||!(0,R.dV)().o.MO)return;const r=ve(this.ee);Ie.tC.forEach((e=>{(0,E.sp)(e,(e=>{a(e)}),!0)}));const n=()=>(0,x.p)("newURL",[(0,S.t)(),""+window.location],void 0,this.featureName,this.ee);r.on("pushState-end",n),r.on("replaceState-end",n);try{this.removeOnAbort=new AbortController}catch(e){}(0,E.sp)("popstate",(e=>(0,x.p)("newURL",[e.timeStamp,""+window.location],void 0,this.featureName,this.ee)),!0,this.removeOnAbort?.signal);let i=!1;const o=new((0,R.dV)().o.MO)(((e,t)=>{i||(i=!0,requestAnimationFrame((()=>{(0,x.p)("newDom",[(0,S.t)()],void 0,this.featureName,this.ee),i=!1})))})),a=(0,v.s)((e=>{(0,x.p)("newUIEvent",[e],void 0,this.featureName,this.ee),o.observe(document.body,{attributes:!0,childList:!0,subtree:!0,characterData:!0})}),100,{leading:!0});this.abortHandler=function(){this.removeOnAbort?.abort(),o.disconnect(),this.abortHandler=void 0},this.importAggregator(e,{domObserver:o})}}var je=i(7378);const Ce={},ke=["appendChild","insertBefore","replaceChild"];function Le(e){const t=function(e){return(e||B.ee).get("jsonp")}(e);if(!p.RI||Ce[t.debugId])return t;Ce[t.debugId]=!0;var r=(0,W.YM)(t),n=/[?&](?:callback|cb)=([^&#]+)/,i=/(.*)\.([^.]+)/,o=/^(\w+)(\.|$)(.*)$/;function a(e,t){if(!e)return t;const r=e.match(o),n=r[1];return a(r[3],t[n])}return r.inPlace(Node.prototype,ke,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var o=(s=e.src,c=s.match(n),c?c[1]:null);var s,c;if(!o)return;var u=function(e){var t=e.match(i);if(t&&t.length>=3)return{key:t[2],parent:a(t[1],window)};return{key:e,parent:window}}(o);if("function"!=typeof u.parent[u.key])return;var d={};function l(){t.emit("jsonp-end",[],d),e.removeEventListener("load",l,(0,E.jT)(!1)),e.removeEventListener("error",f,(0,E.jT)(!1))}function f(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",l,(0,E.jT)(!1)),e.removeEventListener("error",f,(0,E.jT)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",l,(0,E.jT)(!1)),e.addEventListener("error",f,(0,E.jT)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}const He={};function Me(e){const t=function(e){return(e||B.ee).get("promise")}(e);if(He[t.debugId])return t;He[t.debugId]=!0;var r=t.context,n=(0,W.YM)(t),i=p.gm.Promise;return i&&function(){function e(r){var o=t.context(),a=n(r,"executor-",o,null,!1);const s=Reflect.construct(i,[a],e);return t.context(s).getCtx=function(){return o},s}p.gm.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return i.toString()},Object.setPrototypeOf(e,i),["all","race"].forEach((function(r){const n=i[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=i[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=i.prototype;const o=i.prototype.then;i.prototype.then=function(...e){var i=this,a=r(i);a.promise=i,e[0]=n(e[0],"cb-",a,null,!1),e[1]=n(e[1],"cb-",a,null,!1);const s=o.apply(this,e);return a.nextPromise=s,t.emit("propagate",[i,!0],s,!1,!1),s},i.prototype.then[W.Jt]=o,t.on("executor-start",(function(e){e[0]=n(e[0],"resolve-",this,null,!1),e[1]=n(e[1],"resolve-",this,null,!1)})),t.on("executor-err",(function(e,t,r){e[1](r)})),t.on("cb-end",(function(e,r,n){t.emit("propagate",[n,!0],this.nextPromise,!1,!1)})),t.on("propagate",(function(e,r,n){this.getCtx&&!r||(this.getCtx=function(){if(e instanceof Promise)var r=t.context(e);return r&&r.getCtx?r.getCtx():this})}))}(),t}const De={},Ke="setTimeout",Ue="setInterval",Ve="clearTimeout",Ge="-start",Fe=[Ke,"setImmediate",Ue,Ve,"clearImmediate"];function Be(e){const t=function(e){return(e||B.ee).get("timer")}(e);if(De[t.debugId]++)return t;De[t.debugId]=1;var r=(0,W.YM)(t);return r.inPlace(p.gm,Fe.slice(0,2),Ke+"-"),r.inPlace(p.gm,Fe.slice(2,3),Ue+"-"),r.inPlace(p.gm,Fe.slice(3),Ve+"-"),t.on(Ue+Ge,(function(e,t,n){e[0]=r(e[0],"fn-",null,n)})),t.on(Ke+Ge,(function(e,t,n){this.method=n,this.timerDuration=isNaN(e[1])?0:+e[1],e[0]=r(e[0],"fn-",this,n)})),t}const We={};function ze(e){const t=function(e){return(e||B.ee).get("mutation")}(e);if(!p.RI||We[t.debugId])return t;We[t.debugId]=!0;var r=(0,W.YM)(t),n=p.gm.MutationObserver;return n&&(window.MutationObserver=function(e){return this instanceof n?new n(r(e,"fn-")):n.apply(this,arguments)},MutationObserver.prototype=n.prototype),t}const{TZ:qe,d3:Ze,Kp:Ye,$p:Xe,wW:$e,e5:Je,tH:Qe,uP:et,rw:tt,Lc:rt}=je;class nt extends b{static featureName=qe;constructor(e,t=!0){if(super(e,qe,t),!p.RI)return;try{this.removeOnAbort=new AbortController}catch(e){}let r,n=0;const i=this.ee.get("tracer"),o=Le(this.ee),a=Me(this.ee),s=Be(this.ee),c=Z(this.ee),u=this.ee.get("events"),d=ne(this.ee),l=ve(this.ee),f=ze(this.ee);function h(e,t){l.emit("newURL",[""+window.location,t])}function g(){n++,r=window.location.hash,this[et]=(0,S.t)()}function m(){n--,window.location.hash!==r&&h(0,!0);var e=(0,S.t)();this[Je]=~~this[Je]+e-this[et],this[rt]=e}function v(e,t){e.on(t,(function(){this[t]=(0,S.t)()}))}this.ee.on(et,g),a.on(tt,g),o.on(tt,g),this.ee.on(rt,m),a.on($e,m),o.on($e,m),this.ee.on("fn-err",((...t)=>{t[2]?.__newrelic?.[e.agentIdentifier]||(0,x.p)("function-err",[...t],void 0,this.featureName,this.ee)})),this.ee.buffer([et,rt,"xhr-resolved"],this.featureName),u.buffer([et],this.featureName),s.buffer(["setTimeout"+Ye,"clearTimeout"+Ze,et],this.featureName),c.buffer([et,"new-xhr","send-xhr"+Ze],this.featureName),d.buffer([Qe+Ze,Qe+"-done",Qe+Xe+Ze,Qe+Xe+Ye],this.featureName),l.buffer(["newURL"],this.featureName),f.buffer([et],this.featureName),a.buffer(["propagate",tt,$e,"executor-err","resolve"+Ze],this.featureName),i.buffer([et,"no-"+et],this.featureName),o.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),v(d,Qe+Ze),v(d,Qe+"-done"),v(o,"new-jsonp"),v(o,"jsonp-end"),v(o,"cb-start"),l.on("pushState-end",h),l.on("replaceState-end",h),window.addEventListener("hashchange",h,(0,E.jT)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",h,(0,E.jT)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){h(0,n>1)}),(0,E.jT)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#n,this.importAggregator(e)}#n(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}var it=i(3333);class ot extends b{static featureName=it.TZ;constructor(e,t=!0){super(e,it.TZ,t);const r=[e.init.page_action.enabled,e.init.performance.capture_marks,e.init.performance.capture_measures,e.init.user_actions.enabled,e.init.performance.resources.enabled];if(p.RI&&(e.init.user_actions.enabled&&(it.Zp.forEach((e=>(0,E.sp)(e,(e=>(0,x.p)("ua",[e],void 0,this.featureName,this.ee)),!0))),it.qN.forEach((e=>(0,E.sp)(e,(e=>(0,x.p)("ua",[e],void 0,this.featureName,this.ee)))))),e.init.performance.resources.enabled&&p.gm.PerformanceObserver?.supportedEntryTypes.includes("resource"))){new PerformanceObserver((e=>{e.getEntries().forEach((e=>{(0,x.p)("browserPerformance.resource",[e],void 0,this.featureName,this.ee)}))})).observe({type:"resource",buffered:!0})}r.some((e=>e))?this.importAggregator(e):this.deregisterDrain()}}var at=i(993),st=i(3785);class ct extends b{static featureName=at.TZ;constructor(e,t=!0){super(e,at.TZ,t);const r=this.ee;this.ee.on("wrap-logger-end",(function([e]){const{level:t,customAttributes:n}=this;(0,st.R)(r,e,n,t)})),this.importAggregator(e)}}new class extends o{constructor(t,r){super(r),p.gm?(this.features={},(0,R.bQ)(this.agentIdentifier,this),this.desiredFeatures=new Set(t.features||[]),this.desiredFeatures.add(w),this.runSoftNavOverSpa=[...this.desiredFeatures].some((e=>e.featureName===a.K7.softNav)),(0,d.j)(this,t,t.loaderType||"agent"),this.run()):(0,e.R)(21)}get config(){return{info:this.info,init:this.init,loader_config:this.loader_config,runtime:this.runtime}}run(){try{const t=u(this.agentIdentifier),r=[...this.desiredFeatures];r.sort(((e,t)=>a.P3[e.featureName]-a.P3[t.featureName])),r.forEach((r=>{if(!t[r.featureName]&&r.featureName!==a.K7.pageViewEvent)return;if(this.runSoftNavOverSpa&&r.featureName===a.K7.spa)return;if(!this.runSoftNavOverSpa&&r.featureName===a.K7.softNav)return;const n=function(e){switch(e){case a.K7.ajax:return[a.K7.jserrors];case a.K7.sessionTrace:return[a.K7.ajax,a.K7.pageViewEvent];case a.K7.sessionReplay:return[a.K7.sessionTrace];case a.K7.pageViewTiming:return[a.K7.pageViewEvent];default:return[]}}(r.featureName).filter((e=>!(e in this.features)));n.length>0&&(0,e.R)(36,{targetFeature:r.featureName,missingDependencies:n}),this.features[r.featureName]=new r(this)}))}catch(t){(0,e.R)(22,t);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,R.Zm)();delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.features,delete this.sharedAggregator;return r.ee.get(this.agentIdentifier).abort(),!1}}}({features:[he,w,N,Ne,Oe,O,M,ot,ct,Pe,nt],loaderType:"spa"})})()})();</script>
  <meta name="viewport" content="width=device-width, initial-scale=1">
  <meta name="keywords" content="">
  <meta name="description" content="LitMetric - Explore Scientific Literature">
  <!-- css file -->
  <link rel="stylesheet" href="https://www.litmetric.com/css/bootstrap.min.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/ace-responsive-menu.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/menu.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/fontawesome.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/flaticon.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/bootstrap-select.min.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/ud-custom-spacing.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/animate.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/jquery-ui.min.css">
  <link rel="stylesheet" href="https://www.litmetric.com/css/style.css?v=1.28">
  <!-- Responsive stylesheet -->
  <link rel="stylesheet" href="https://www.litmetric.com/css/responsive.css">
  <!-- Title -->
    <title>Publications by Timea Besenyei | LitMetric</title>
  <!-- Favicon -->
  <link href="https://www.litmetric.com/images/favicon.ico?v=1.1" sizes="128x128" rel="shortcut icon" type="image/x-icon" />
  <link href="https://www.litmetric.com/images/favicon.ico?v=1.1" sizes="128x128" rel="shortcut icon" />
  <!-- Apple Touch Icon -->
  <link href="https://www.litmetric.com/images/apple-touch-icon-60x60.png?v=1.1" sizes="60x60" rel="apple-touch-icon">
  <link href="https://www.litmetric.com/images/apple-touch-icon-72x72.png?v=1.1" sizes="72x72" rel="apple-touch-icon">
  <link href="https://www.litmetric.com/images/apple-touch-icon-114x114.png?v=1.1" sizes="114x114" rel="apple-touch-icon">
  <link href="https://www.litmetric.com/images/apple-touch-icon-180x180.png?v=1.1" sizes="180x180" rel="apple-touch-icon">
  
  <!-- HTML5 shim and Respond.js for IE8 support of HTML5 elements and media queries -->
  <!-- WARNING: Respond.js doesn't work if you view the page via file:// -->
  <!--[if lt IE 9]>
  <script src="https://oss.maxcdn.com/html5shiv/3.7.3/html5shiv.min.js"></script>
  <script src="https://oss.maxcdn.com/respond/1.4.2/respond.min.js"></script>
  <![endif]-->

  </head>
  <body>
  <div class="wrapper ovh">
 <!--   <div class="preloader"></div> -->
    
    <!-- Main Header Nav -->
    <header class="header-nav nav-innerpage-style main-menu">
      <!-- Ace Responsive Menu -->
      <nav class="posr"> 
        <div class="container-fluid posr menu_bdrt1">
          <div class="row align-items-center justify-content-between">
            <div class="col-auto pe-0">
              <div class="d-flex align-items-center">
        <a class="header-logo bdrr1 pr30 pr5-xl" href="https://www.litmetric.com/home"><img src="https://www.litmetric.com/images/header-logo-dark.png" alt="LitMetric"></a>
                <div class="home1_style">
                  <div id="mega-menu">
                    <a class="btn-mega fw500" href="https://www.litmetric.com/categories"><span class="pl30 pl10-xl pr5 fz15 vam flaticon-menu"></span>Article  Categories</a>
                    
               <ul class="menu ps-0"><li> <a class="dropdown" href="https://www.litmetric.com/categories/Allergy+and+Immunology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Allergy and Immunology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Cardiology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Cardiology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Clinical+Procedures"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Clinical Procedures</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Critical+Care"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Critical Care</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Dermatology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Dermatology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Emergency+Medicine"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Emergency Medicine</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Endocrinology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Endocrinology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Gastroenterology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Gastroenterology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Genomic+Medicine"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Genomic Medicine</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Hematology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Hematology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Infectious+Diseases"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Infectious Diseases</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Nephrology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Nephrology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Neurology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Neurology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Obstetrics+and+Gynecology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Obstetrics and Gynecology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Oncology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Oncology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Pathology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Pathology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Perioperative+Care"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Perioperative Care</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Physical+Medicine+and+Rehabilitation"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Physical & Rehabilitation</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Psychiatry"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Psychiatry</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Pulmonology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Pulmonology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Radiology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Radiology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Rheumatology"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Rheumatology</span> </a>
                   </li><li> <a class="dropdown" href="https://www.litmetric.com/categories/Sports+Medicine"> <span class="menu-icn flaticon-badge"></span>
               <span class="menu-title">Sports Medicine</span> </a>
                   </li></ul>
                  
                  
                  
                  
                  </div>
                </div>
              </div>
            </div>
            <div class="col-auto">
              <div class="d-flex align-items-center">
                <!-- Responsive Menu Structure-->
                <ul id="respMenu" class="ace-responsive-menu" data-menu-style="horizontal">
                 
                
                <li> <a class="list-item" href="https://www.litmetric.com/categories">Browse Categories</a></li>
                <li> <a class="list-item" href="https://www.litmetric.com/drugs">Browse Drugs</a></li>
                <li> <a class="list-item" href="https://www.litmetric.com/journals">Browse Journals</a></li>
           <!--     <li> <a class="list-item" href="https://www.litmetric.com/authors">Browse Authors</a></li>-->
                </ul>
                <a class="login-info bdrl1 pl15-lg pl30" data-bs-toggle="modal" href="#exampleModalToggle" role="button"><span class="flaticon-loupe"></span></a>
                <div class="login-info mx15-lg mx30" class="login-info mr15-lg mr30"></div>
 <!--
                <a class="login-info mx15-lg mx30" class="login-info mr15-lg mr30" href="page-login.html">Sign in</a>
                <a class="ud-btn btn-thm add-joining" href="page-register.html">Join</a>
                
              -->
              </div>
            </div>
          </div>
        </div>
      </nav>
    </header>



            
            <!-- Search Modal -->
            <div class="search-modal">
              
              <form action="https://www.litmetric.com/search" method="post" >
              <div class="modal fade" id="exampleModalToggle" aria-hidden="true" aria-labelledby="exampleModalToggleLabel" tabindex="-1">
                <div class="modal-dialog modal-lg">
                  <div class="modal-content">
                    <div class="modal-header">
                      <h5 class="modal-title" id="exampleModalToggleLabel"></h5>
                      <button type="button" class="btn-close" data-bs-dismiss="modal" aria-label="Close"><i class="fal fa-xmark"></i></button>
                    </div>
                    <div class="modal-body">
                      <div class="popup-search-field search_area">
                        <input type="text" class="form-control border-0" placeholder="Article title or keywords" name="searchterm" >
                        <label><span class="far fa-magnifying-glass"></span></label>
                        <button class="ud-btn btn-thm" type="submit">Search</button>
                       
                      </div>
                    </div>
                  </div>
                </div>
              </div>
              </form>
            </div>
            
            <div class="hiddenbar-body-ovelay"></div>
            
       <!-- Mobile Nav  -->
<div id="page" class="mobilie_header_nav stylehome1">
  <div class="mobile-menu">
    <div class="header bdrb1">
      <div class="menu_and_widgets">
        <div class="mobile_menu_bar d-flex justify-content-between align-items-center">
          <a class="mobile_logo" href="https://www.litmetric.com/"><img src="https://www.litmetric.com/images/header-logo-dark.png" alt=""></a>
          <div class="right-side text-end">
            
              <a class="" href="https://www.litmetric.com/categories">Browse Categories</a>



            <a class="menubar ml30" href="#menu"><img src="https://www.litmetric.com/images/mobile-dark-nav-icon.svg" alt=""></a>
          </div>
        </div>
      </div>
      <div class="posr"><div class="mobile_menu_close_btn"><span class="far fa-times"></span></div></div>
    </div>
  </div>
  <!-- /.mobile-menu -->
  <nav id="menu" class="">
    <ul>
      <li><span><a href="https://www.litmetric.com/categories">Browse Categories</a></span>
        <ul>
	        <li><a  href="https://www.litmetric.com/categories/Allergy+and+Immunology">Allergy and Immunology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Cardiology">Cardiology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Clinical+Procedures">Clinical Procedures</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Critical+Care">Critical Care</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Dermatology">Dermatology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Emergency+Medicine">Emergency Medicine</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Endocrinology">Endocrinology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Gastroenterology">Gastroenterology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Genomic+Medicine">Genomic Medicine</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Hematology">Hematology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Infectious+Diseases">Infectious Diseases</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Nephrology">Nephrology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Neurology">Neurology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Obstetrics+and+Gynecology">Obstetrics and Gynecology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Oncology">Oncology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Pathology">Pathology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Perioperative+Care">Perioperative Care</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Physical+Medicine+and+Rehabilitation">Physical & Rehabilitation</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Psychiatry">Psychiatry</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Pulmonology">Pulmonology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Radiology">Radiology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Rheumatology">Rheumatology</a></li>
	        <li> <a  href="https://www.litmetric.com/categories/Sports+Medicine">Sports Medicine</a></li>
	        </ul>
                   
      </li>
      <li><span><a href="https://www.litmetric.com/journals">Browse Journals</a></span>
      <ul>
	        <li></li>
	        </ul>
	        
      </li>
      <!-- Only for Mobile View -->
    </ul>
  </nav>
</div>


 
        
        
         
            <div class="body_content bgc-thm3">
              
               
     
              <!-- Breadcumb Sections -->
              <section class="breadcumb-section">
                <div class="container">
                  <div class="row">
                     
                                  
                  </div>
                </div>
              </section>
              
   
                        



   

<script type="application/ld+json">
    {
      "@context": "http://schema.org",
      "@type": "Person",

      "name": "Timea Besenyei",


      "url": "https://www.litmetric.com/author/Timea+Besenyei"

    }
    </script>


  
   
   <!-- Breadcumb Sections -->
   <section class="breadcumb-section pt-0">
     <div class="cta-service-v1 freelancer-single-style mx-auto maxw1700 pt20 pt60-sm pb20 pb60-sm bdrs16 position-relative overflow-hidden d-flex align-items-center mx20-lg px30-lg" style="height:auto">
       <img class="left-top-img wow zoomIn" src="https://www.litmetric.com/images/vector-img/left-top.png" alt="">
       <img class="right-bottom-img wow zoomIn" src="https://www.litmetric.com/images/vector-img/right-bottom.png" alt="">
       <div class="container">
         <div class="row wow fadeInUp">
           <div class="col-xl-10">
             <div class="position-relative">
               <h2>Publications by authors named "Timea Besenyei"</h2>
               <div class="list-meta d-sm-flex align-items-center mt15">
             
          <!--       <div class="ml5 ml0-xs">
            
                    <p class="mb-0 dark-color fz15 fw500 list-inline-item ml15 mb5-sm ml0-xs"><i class="flaticon-contract vam fz20 me-2"></i> </p>
              
                   <p class="mb-0 dark-color fz15 fw500 list-inline-item mr15  mb5-sm ml0-xs"><i class="flaticon-place text-thm2 vam fz20 me-2"></i> </p>
                 </div>
               -->
               </div>
             </div>
           </div>
         </div>
       </div>
     </div>
   </section>
   
   
   
   <!-- Service Details -->
   <section class="pt10 pb90 pb30-md">
     <div class="container">
      
        
        
       <div class="row wow fadeInUp">
	       
    <div class="col-lg-12">
                     
                                     <div class="mbp_pagination text-right"><ul class="page_navigation" style="text-align:right"><li class="page-item" style="border:none;">Page <strong>1</strong> of <strong>1</strong></li></ul></div> 
                          
                          <!--
                            <div class="publication-title-box">
                            <p><strong></strong>Reads</p>
                          </div>
                           <div class="publication-title-box">
                            <p><strong></strong>Profile Views</p>
                          </div>
                          -->
                     
                       </div>
                       
             
                                        
         <div class="col-lg-12">
                           
           <div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/30987671/Gene-expression-analysis-of-vascular-pathophysiology-related-to-anti-TNF-treatment-in-rheumatoid-art">Gene expression analysis of vascular pathophysiology related to anti-TNF treatment in rheumatoid arthritis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Szilard+Poliska" class="tag" style="margin-bottom: 5px;">Szilárd Póliska</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Edit+Vegh" class="tag" style="margin-bottom: 5px;">Edit Végh</a> <a href="https://www.litmetric.com/author/Attila+Hamar" class="tag" style="margin-bottom: 5px;">Attila Hamar</a> <a href="https://www.litmetric.com/author/Anita+Pusztai" class="tag" style="margin-bottom: 5px;">Anita Pusztai</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Arthritis Res Ther</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> April 2019</p></div>
								 </div><p class="text mt10"><em>Objectives</em>: Impaired vascular pathophysiology and increased cardiovascular (CV) mortality are associated with rheumatoid arthritis (RA). To date, no genomic analysis of RA- and RA treatment-related vascular pathophysiology has been published. In this pilot study, we performed gene expression profiling in association with vascular pathophysiology in RA patients.</p><a href="https://www.litmetric.com/detail/30987671/Gene-expression-analysis-of-vascular-pathophysiology-related-to-anti-TNF-treatment-in-rheumatoid-art" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/23653330/Differentially-expressed-epigenome-modifiers-including-aurora-kinases-A-and-B-in-immune-cells-in-rhe">Differentially expressed epigenome modifiers, including aurora kinases A and B, in immune cells in rheumatoid arthritis in humans and mouse models.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Tibor+T+Glant" class="tag" style="margin-bottom: 5px;">Tibor T Glant</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Andras+Kadar" class="tag" style="margin-bottom: 5px;">András Kádár</a> <a href="https://www.litmetric.com/author/Julia+Kurko" class="tag" style="margin-bottom: 5px;">Júlia Kurkó</a> <a href="https://www.litmetric.com/author/Beata+Tryniszewska" class="tag" style="margin-bottom: 5px;">Beata Tryniszewska</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Arthritis Rheum</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> July 2013</p></div>
								 </div><p class="text mt10"><em>Objective</em>: To identify epigenetic factors that are implicated in the pathogenesis of rheumatoid arthritis (RA), and to explore the therapeutic potential of the targeted inhibition of these factors.<BR><BR><em>Methods</em>: Polymerase chain reaction (PCR) arrays were used to investigate the expression profile of genes that encode key epigenetic regulator enzymes. Mononuclear cells from RA patients and mice were monitored for gene expression changes, in association with arthritis development in murine models of RA.</p><a href="https://www.litmetric.com/detail/23653330/Differentially-expressed-epigenome-modifiers-including-aurora-kinases-A-and-B-in-immune-cells-in-rhe" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/23564183/Pharmacogenetics-and-pharmacogenomics-in-rheumatology">Pharmacogenetics and pharmacogenomics in rheumatology.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zoltan+Szekanecz" class="tag" style="margin-bottom: 5px;">Zoltán Szekanecz</a> <a href="https://www.litmetric.com/author/Bertalan+Mesko" class="tag" style="margin-bottom: 5px;">Bertalan Meskó</a> <a href="https://www.litmetric.com/author/Szilard+Poliska" class="tag" style="margin-bottom: 5px;">Szilard Poliska</a> <a href="https://www.litmetric.com/author/Andrea+Vancsa" class="tag" style="margin-bottom: 5px;">Andrea Váncsa</a> <a href="https://www.litmetric.com/author/Szilvia+Szamosi" class="tag" style="margin-bottom: 5px;">Szilvia Szamosi</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Immunol Res</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> July 2013</p></div>
								 </div><p class="text mt10">Pharmacogenetics and pharmacogenomics deal with possible associations of a single genetic polymorphism or those of multiple gene profiles with responses to drugs. In rheumatology, genes and gene signatures may be associated with altered efficacy and/or safety of anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs) and biologics. In brief, genes of cytochrome P450, other enzymes involved in drug metabolism, transporters and some cytokines have been associated with responses to and toxicity of non-steroidal anti-inflammatory drugs, corticosteroids and DMARDs.</p><a href="https://www.litmetric.com/detail/23564183/Pharmacogenetics-and-pharmacogenomics-in-rheumatology" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/23288628/Genetics-of-rheumatoid-arthritis-a-comprehensive-review">Genetics of rheumatoid arthritis - a comprehensive review.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Julia+Kurko" class="tag" style="margin-bottom: 5px;">Júlia Kurkó</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Judit+Laki" class="tag" style="margin-bottom: 5px;">Judit Laki</a> <a href="https://www.litmetric.com/author/Tibor+T+Glant" class="tag" style="margin-bottom: 5px;">Tibor T Glant</a> <a href="https://www.litmetric.com/author/Katalin+Mikecz" class="tag" style="margin-bottom: 5px;">Katalin Mikecz</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Clin Rev Allergy Immunol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> October 2013</p></div>
								 </div><p class="text mt10">The "Bermuda triangle" of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11-37 %.</p><a href="https://www.litmetric.com/detail/23288628/Genetics-of-rheumatoid-arthritis-a-comprehensive-review" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/23251214/Non-MHC-risk-alleles-in-rheumatoid-arthritis-and-in-the-syntenic-chromosome-regions-of-corresponding">Non-MHC risk alleles in rheumatoid arthritis and in the syntenic chromosome regions of corresponding animal models.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Andras+Kadar" class="tag" style="margin-bottom: 5px;">Andras Kadar</a> <a href="https://www.litmetric.com/author/Beata+Tryniszewska" class="tag" style="margin-bottom: 5px;">Beata Tryniszewska</a> <a href="https://www.litmetric.com/author/Julia+Kurko" class="tag" style="margin-bottom: 5px;">Julia Kurko</a> <a href="https://www.litmetric.com/author/Tibor+A+Rauch" class="tag" style="margin-bottom: 5px;">Tibor A Rauch</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Clin Dev Immunol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> August 2013</p></div>
								 </div><p class="text mt10">Rheumatoid arthritis (RA) is a polygenic autoimmune disease primarily affecting the synovial joints. Numerous animal models show similarities to RA in humans; some of them not only mimic the clinical phenotypes but also demonstrate the involvement of homologous genomic regions in RA. This paper compares corresponding non-MHC genomic regions identified in rodent and human genome-wide association studies (GWAS).</p><a href="https://www.litmetric.com/detail/23251214/Non-MHC-risk-alleles-in-rheumatoid-arthritis-and-in-the-syntenic-chromosome-regions-of-corresponding" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/22492217/Suppression-of-dendritic-cell-maturation-and-T-cell-proliferation-by-synovial-fluid-myeloid-cells-fr">Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Colt+Egelston" class="tag" style="margin-bottom: 5px;">Colt Egelston</a> <a href="https://www.litmetric.com/author/Julia+Kurko" class="tag" style="margin-bottom: 5px;">Júlia Kurkó</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Beata+Tryniszewska" class="tag" style="margin-bottom: 5px;">Beata Tryniszewska</a> <a href="https://www.litmetric.com/author/Tibor+A+Rauch" class="tag" style="margin-bottom: 5px;">Tibor A Rauch</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Arthritis Rheum</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> October 2012</p></div>
								 </div><p class="text mt10"><em>Objective</em>: To determine whether myeloid cells (such as granulocytes) present in the synovial fluid (SF) of arthritic joints have an impact on adaptive immunity. Specifically, we investigated the effects of SF cells harvested from the joints of mice with proteoglycan-induced arthritis (PGIA), on dendritic cell (DC) maturation and antigen-specific T cell proliferation.<BR><BR><em>Methods</em>: We monitored DC maturation (MHCII and CD86 expression) by flow cytometry upon coculture of DCs with SF cells or spleen myeloid cells from mice with PGIA.</p><a href="https://www.litmetric.com/detail/22492217/Suppression-of-dendritic-cell-maturation-and-T-cell-proliferation-by-synovial-fluid-myeloid-cells-fr" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/21733730/Associations-of-HLA-shared-epitope-anti-citrullinated-peptide-antibodies-and-lifestyle-related-facto">Associations of HLA-shared epitope, anti-citrullinated peptide antibodies and lifestyle-related factors in Hungarian patients with rheumatoid arthritis: data from the first Central-Eastern European cohort.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Agnes+Gyetvai" class="tag" style="margin-bottom: 5px;">Agnes Gyetvai</a> <a href="https://www.litmetric.com/author/Zoltan+Szabo" class="tag" style="margin-bottom: 5px;">Zoltán Szabó</a> <a href="https://www.litmetric.com/author/Andrea+Fekete" class="tag" style="margin-bottom: 5px;">Andrea Fekete</a> <a href="https://www.litmetric.com/author/Aniko+Kapitany" class="tag" style="margin-bottom: 5px;">Anikó Kapitány</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Joint Bone Spine</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> December 2011</p></div>
								 </div><p class="text mt10"></p><a href="https://www.litmetric.com/detail/21733730/Associations-of-HLA-shared-epitope-anti-citrullinated-peptide-antibodies-and-lifestyle-related-facto" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/20305562/Angiogenesis-and-vasculogenesis-in-rheumatoid-arthritis">Angiogenesis and vasculogenesis in rheumatoid arthritis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zoltan+Szekanecz" class="tag" style="margin-bottom: 5px;">Zoltán Szekanecz</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Agnes+Szentpetery" class="tag" style="margin-bottom: 5px;">Agnes Szentpétery</a> <a href="https://www.litmetric.com/author/Alisa+E+Koch" class="tag" style="margin-bottom: 5px;">Alisa E Koch</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Curr Opin Rheumatol</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> May 2010</p></div>
								 </div><p class="text mt10"><em>Purpose Of Review</em>: Angiogenesis is the formation of new capillaries from pre-existing vessels, whereas vasculogenesis is de-novo capillary formation from endothelial precursor cells (EPCs). Current understanding of the role of angiogenesis and vasculogenesis in rheumatoid arthritis (RA) and possibilities of therapeutic intervention should be summarized.<BR><BR><em>Recent Findings</em>: There have been many recent studies on the role of the hypoxia and hypoxia-inducible factor (HIF)-vascular endothelial growth factor (VEGF)-angiopoietin axis in angiogenesis associated with RA.</p><a href="https://www.litmetric.com/detail/20305562/Angiogenesis-and-vasculogenesis-in-rheumatoid-arthritis" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/20022538/New-insights-in-synovial-angiogenesis">New insights in synovial angiogenesis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zoltan+Szekanecz" class="tag" style="margin-bottom: 5px;">Zoltán Szekanecz</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Gyoergy+Paragh" class="tag" style="margin-bottom: 5px;">György Paragh</a> <a href="https://www.litmetric.com/author/Alisa+E+Koch" class="tag" style="margin-bottom: 5px;">Alisa E Koch</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Joint Bone Spine</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> January 2010</p></div>
								 </div><p class="text mt10">Angiogenesis is the formation of new capillaries from pre-existing vessels. A number of soluble and cell-bound factors may stimulate neovascularization. The perpetuation of angiogenesis involving numerous soluble and cell surface-bound mediators has been associated with rheumatoid arthritis (RA).</p><a href="https://www.litmetric.com/detail/20022538/New-insights-in-synovial-angiogenesis" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/19945323/Endothelial-progenitor-cells-in-arthritis-associated-vasculogenesis-and-atherosclerosis">Endothelial progenitor cells in arthritis-associated vasculogenesis and atherosclerosis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Angela+Pakozdi" class="tag" style="margin-bottom: 5px;">Angéla Pákozdi</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Gyoergy+Paragh" class="tag" style="margin-bottom: 5px;">György Paragh</a> <a href="https://www.litmetric.com/author/Alisa+E+Koch" class="tag" style="margin-bottom: 5px;">Alisa E Koch</a> <a href="https://www.litmetric.com/author/Zoltan+Szekanecz" class="tag" style="margin-bottom: 5px;">Zoltán Szekanecz</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Joint Bone Spine</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> December 2009</p></div>
								 </div><p class="text mt10">Vasculogenesis is the generation of vessels from endothelial progenitor cells (EPCs). Attenuated numbers and function of EPCs associated with defective vasculogenesis are present in rheumatoid arthritis (RA), scleroderma and other autoimmune-inflammatory diseases, which have significant relevance for increased cardio- and cerebrovascular morbidity and mortality in arthritis [–5]. Stimulation of EPCs and vasculogenesis may be beneficial to prevent and manage atherosclerosis related to arthritis.</p><a href="https://www.litmetric.com/detail/19945323/Endothelial-progenitor-cells-in-arthritis-associated-vasculogenesis-and-atherosclerosis" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/19863375/Angiogenesis-in-rheumatoid-arthritis">Angiogenesis in rheumatoid arthritis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zoltan+Szekanecz" class="tag" style="margin-bottom: 5px;">Zoltán Szekanecz</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Gyoergy+Paragh" class="tag" style="margin-bottom: 5px;">György Paragh</a> <a href="https://www.litmetric.com/author/Alisa+E+Koch" class="tag" style="margin-bottom: 5px;">Alisa E Koch</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Autoimmunity</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> November 2009</p></div>
								 </div><p class="text mt10">Angiogenesis is the formation of new capillaries from pre-existing vessels. A number of soluble and cell-bound factors may stimulate neovascularization. The perpetuation of angiogenesis involving numerous soluble and cell surface-bound mediators has been associated with rheumatoid arthritis (RA).</p><a href="https://www.litmetric.com/detail/19863375/Angiogenesis-in-rheumatoid-arthritis" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/19482623/Chemokines-and-angiogenesis-in-rheumatoid-arthritis">Chemokines and angiogenesis in rheumatoid arthritis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zoltan+Szekanecz" class="tag" style="margin-bottom: 5px;">Zoltan Szekanecz</a> <a href="https://www.litmetric.com/author/Angela+Pakozdi" class="tag" style="margin-bottom: 5px;">Angela Pakozdi</a> <a href="https://www.litmetric.com/author/Agnes+Szentpetery" class="tag" style="margin-bottom: 5px;">Agnes Szentpetery</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a> <a href="https://www.litmetric.com/author/Alisa+E+Koch" class="tag" style="margin-bottom: 5px;">Alisa E Koch</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Front Biosci (Elite Ed)</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> June 2009</p></div>
								 </div><p class="text mt10">In rheumatoid arthritis, chemokines mediate the migration of inflammatory leukocytes into the synovium. Among the four known chemokine families, CXC, CC chemokines and fractalkine seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important during the perpetuation of inflammation underlying rheumatoid arthritis.</p><a href="https://www.litmetric.com/detail/19482623/Chemokines-and-angiogenesis-in-rheumatoid-arthritis" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/17893999/Increased-production-of-the-soluble-tumor-associated-antigens-CA19-9-CA125-and-CA15-3-in-rheumatoid-">Increased production of the soluble tumor-associated antigens CA19-9, CA125, and CA15-3 in rheumatoid arthritis: potential adhesion molecules in synovial inflammation?</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Eva+Szekanecz" class="tag" style="margin-bottom: 5px;">Eva Szekanecz</a> <a href="https://www.litmetric.com/author/Zsuzsa+Sandor" class="tag" style="margin-bottom: 5px;">Zsuzsa Sándor</a> <a href="https://www.litmetric.com/author/Peter+Antal-Szalmas" class="tag" style="margin-bottom: 5px;">Péter Antal-Szalmás</a> <a href="https://www.litmetric.com/author/Lilla+Soos" class="tag" style="margin-bottom: 5px;">Lilla Soós</a> <a href="https://www.litmetric.com/author/Gabriella+Lakos" class="tag" style="margin-bottom: 5px;">Gabriella Lakos</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Ann N Y Acad Sci</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> June 2007</p></div>
								 </div><p class="text mt10">Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected carcinoembryonic antigen (CEA; CD66) in the rheumatoid (RA) synovium. The production of CEA, CA19-9, CA125, and CA15.</p><a href="https://www.litmetric.com/detail/17893999/Increased-production-of-the-soluble-tumor-associated-antigens-CA19-9-CA125-and-CA15-3-in-rheumatoid-" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div><div class="col-md-6 col-lg-12" >
			 <div class="freelancer-style1 bdr1 bdrs12 hover-box-shadow row ms-0 align-items-lg-center">
			   <div class="col-lg-12 ps-0">
				 <div class="d-lg-flex">
				   <div class="thumb w60 position-relative rounded-circle mb15-md">
				 
					 
					 <i class="flaticon-document text-thm2 pe-2 vam" style="font-size: 60px;"></i>
				   </div>
				   <div class="details ml15 ml0-md mb15-md">
					 <h5 class="title mb-3"><a href="https://www.litmetric.com/detail/17893998/Accelerated-atherosclerosis-in-rheumatoid-arthritis">Accelerated atherosclerosis in rheumatoid arthritis.</a></h5><div class="publication-auther"><a href="https://www.litmetric.com/author/Zoltan+Szekanecz" class="tag" style="margin-bottom: 5px;">Zoltán Szekanecz</a> <a href="https://www.litmetric.com/author/Gyoergy+Kerekes" class="tag" style="margin-bottom: 5px;">György Kerekes</a> <a href="https://www.litmetric.com/author/Henriett+Der" class="tag" style="margin-bottom: 5px;">Henriett Dér</a> <a href="https://www.litmetric.com/author/Zsuzsa+Sandor" class="tag" style="margin-bottom: 5px;">Zsuzsa Sándor</a> <a href="https://www.litmetric.com/author/Zoltan+Szabo" class="tag" style="margin-bottom: 5px;">Zoltán Szabó</a> <a href="https://www.litmetric.com/author/Timea+Besenyei" class="tag" style="margin-bottom: 5px;">Timea Besenyei</a></div><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-contract fz16 vam text-thm2 me-1"></i> Ann N Y Acad Sci</p><p class="mb-0 fz14 list-inline-item mb5-sm pe-1"><i class="flaticon-calendar fz16 vam text-thm2 me-1 bdrl1 pl15 pl0-xs bdrn-xs"></i> June 2007</p></div>
								 </div><p class="text mt10">Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. Both traditional, Framingham risk factors and inflammation-associated factors are involved in RA-associated atherosclerosis.</p><a href="https://www.litmetric.com/detail/17893998/Accelerated-atherosclerosis-in-rheumatoid-arthritis" class="ud-btn btn-thm mb25 me-4 "><i class="flaticon-contract fz16 vam text-thm2 me-1" style="color:white"></i> View Article and Find Full Text PDF <i class="fal fa-arrow-right-long"></i></a><div class="skill-tags d-flex align-items-center justify-content-start mb20-md"></div></div>
    </div></div>           <div class="row">
           
                          </div>
         </div>

              
                         
     </div>
   </section>
   
   

          



    <!-- Our Footer --> 
    <section class="footer-style1 pt25 pb-0">
      <div class="container">
        <div class="row  pb10">
          <div class="col-md-7">
            <div class="d-block text-center text-md-start justify-content-center justify-content-md-start d-md-flex align-items-center mb-3 mb-md-0">
              <a class="fz17 fw500 text-white mr15-md mr30" href="https://www.litmetric.com/privacypolicy">Privacy Policy</a>
              <a class="fz17 fw500 text-white" href="https://www.litmetric.com/sitemap">Site Map</a>
            </div>
          </div>
          <div class="col-md-5">
            <div class="social-widget text-center text-md-end">
              <div class="social-style1">
                <a class="text-white me-2 fw500 fz17" href="mailto:info@litmetric.com">Contact Us</a>
                <!--
                <a href=""><i class="fab fa-facebook-f list-inline-item"></i></a>
                <a href=""><i class="fab fa-twitter list-inline-item"></i></a>
                <a href=""><i class="fab fa-instagram list-inline-item"></i></a>
                <a href=""><i class="fab fa-linkedin-in list-inline-item"></i></a>
              -->
              </div>
            </div>
          </div>
        </div>
              </div>
      <div class="container white-bdrt1 py-4">
        <div class="row align-items-center">
          <div class="col-md-12">
            <div class="text-center text-lg-start">
              <p class="copyright-text mb-2 mb-md-0 text-white-light ff-heading">© LitMetric 2024. All rights reserved.</p>
            </div>
          </div>
    
        </div>
      </div>
    </section>
    <a class="scrollToHome" href="#"><i class="fas fa-angle-up"></i></a>
  </div>
</div>
<!-- Wrapper End --> 
<script src="https://www.litmetric.com/js/jquery-3.6.4.min.js"></script>
<script src="https://www.litmetric.com/js/jquery-migrate-3.0.0.min.js"></script>
<script src="https://www.litmetric.com/js/popper.min.js"></script>
<script src="https://www.litmetric.com/js/bootstrap.min.js"></script>
<script src="https://www.litmetric.com/js/bootstrap-select.min.js"></script>
<script src="https://www.litmetric.com/js/jquery.mmenu.all.js"></script>
  
  

<script src="https://www.litmetric.com/js/ace-responsive-menu.js"></script>
<script src="https://www.litmetric.com/js/jquery-scrolltofixed-min.js"></script>
<script src="https://www.litmetric.com/js/wow.min.js"></script>
<script src="https://www.litmetric.com/js/scrollbalance.js"></script>
<!-- Custom script for all pages --> 
<script src="https://www.litmetric.com/js/script.js?v=1.47"></script>
</body>
</html>

      <script type="text/javascript">  
	    
	    
	    
	      


      

      

      
    
    
</script>

<script>
//  Fixed sidebar Custom Script For That 
$(function() {
  var cols = $('.wrap .column');
  var enabled = true;
  var scrollbalance = new ScrollBalance(cols, {
    minwidth: 1199
  });
  // bind to scroll and resize events
  scrollbalance.bind();
}); 



</script>




<script type="text/javascript">window.NREUM||(NREUM={});NREUM.info={"beacon":"bam.nr-data.net","licenseKey":"NRJS-750ae8097b9f1344f1a","applicationID":"589630826","transactionName":"ZVZbN0FZXEtUAENfV1wcbBFaF1tWUQZPGEhaQw==","queueTime":0,"applicationTime":627,"atts":"SRFYQQlDT0U=","errorBeacon":"bam.nr-data.net","agent":""}</script></body>
</html>