Predictive value of anti-CarP and anti-PAD3 antibodies alone or in combination with RF and ACPA for the severity of rheumatoid arthritis.

Objectives: The objective of this study was to analyse the predictive value of anti-carbamylated protein (anti-CarP) and anti-peptidyl-arginine deiminase type-3 (anti-PAD3) antibodies, alone or in combination with RF and ACPA, to identify patients at high risk of developing severe RA outcomes.

Methods: Patients within the Swiss Clinical Quality Management registry with a biobank sample were tested for RF, ACPA, anti-CarP, and anti-PAD3 antibodies. We examined the association of each autoantibody with DAS28, HAQ and radiographic damage (Ratingen) at baseline and longitudinally.

Presence of IL-17 in synovial fluid identifies a potential inflammatory osteoarthritic phenotype.

Purpose: Osteoarthritis (OA) is a common and heterogeneous arthritic disorder. Patients suffer pain and their joints are characterized by articular cartilage loss and osteophyte formation. Risk factors for OA include age and obesity with inflammation identified as a key mediator of disease pathogenesis.

The prevalence of anticitrullinated protein antibodies increases with age in healthy individuals at risk for rheumatoid arthritis.

Transition from genetic risk to the development of systemic autoimmunity associated with rheumatoid arthritis (RA) is considered a key step for the development of RA and often referred to as the immune onset of the disease. The aim of this study is to identify predictors for the presence of anticitrullinated protein antibodies (ACPA) as a marker of systemic autoimmunity associated with RA in a high-risk population, an ongoing cohort of first-degree relatives of patients with RA. We assessed the presence of ACPA in individuals without clinical evidence of RA.

Elevated serum levels of free interleukin-18 in adult-onset Still's disease.

Objective: IL-18 is a pro-inflammatory cytokine of the IL-1 family that is naturally inhibited by IL-18 binding protein (IL-18BP). High levels of IL-18 have been described in the serum of adult-onset Still's disease (AOSD) patients, but only total IL-18 levels (including inactive IL-18 bound to IL-18BP) have been measured. With a specific immunoassay, we aimed to measure free IL-18 serum levels in AOSD patients and other rheumatic diseases.

Adipokines correlate with pain in lower limb osteoarthritis: different associations in hip and knee.

Purpose: Our aim was to investigate whether serum and synovial-fluid (SF) concentrations of interleukin-6 (IL-6), leptin, adiponectin, resistin or visfatin are associated with joint pain in hip and knee in end-stage osteoarthritis (OA).

Methods: A cross-sectional study assessing patients with hip and knee OA undergoing total joint arthroplasty between January and December 2010 was conducted at a large university hospital. Serum and SF cytokine and adipokine concentrations were determined in samples obtained on the day of surgery.

Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout.

Objective: Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known.

Do synovial leptin levels correlate with pain in end stage arthritis?

Purpose: We evaluated whether synovial fluid (SF) leptin concentrations correlate with pain severity in patients with hip or knee endstage osteoarthritis (OA) and whether they mediate the association between increased joint pain and (1) female gender and (2) obesity.

Methods: We conducted a cross-sectional study including patients with primary hip and knee OA undergoing joint replacement between January and December 2010. SF leptin concentrations obtained on the day of surgery were assessed.

Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease.

Introduction: The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans.

Evaluation of cardiovascular risk in patients with rheumatoid arthritis: do cardiovascular biomarkers offer added predictive ability over established clinical risk scores?

Objective: To determine whether adding C-reactive protein, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, N-terminal pro-brain natriuretic peptide (NT-proBNP), oxidized low-density lipoprotein (ox-LDL), or anti-apolipoprotein A-I (anti-Apo A-I) IgG to the Framingham 10-year cardiovascular (CV) risk score (FRS) could improve its CV prognostic accuracy in rheumatoid arthritis (RA).

Methods: We performed an ancillary study derived from a prospective single-center cohort consisting of 118 RA patients without CV disease at baseline. The FRS and the various biomarkers were assessed at enrollment and their prognostic accuracy was determined using receiver operating characteristic (ROC) curve analysis.

Distinct serum and synovial fluid interleukin (IL)-33 levels in rheumatoid arthritis, psoriatic arthritis and osteoarthritis.

Objectives: Recent evidence suggests a role for interleukin (IL)-33 and its receptor ST2 in arthritis. In this study, we quantified IL-33 and soluble (s)ST2 levels in serum and synovial fluid (SF), and assessed synovial IL-33 expression levels and pattern in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or osteoarthritis (OA).

Methods: Serum and SF IL-33 and sST2 levels were assessed by ELISA.

Spontaneous secretion of interleukin-17 and -22 by human cervical cells in Chlamydia trachomatis infection.

To investigate whether IL-17A (IL-17) and IL-22 are produced in response to Chlamydia trachomatis infection, the cervical washes of 27 women with C. trachomatis infection and 17 C. trachomatis negative controls were collected.

Serum lipoproteins attenuate macrophage activation and Toll-Like Receptor stimulation by bacterial lipoproteins.

Background: Chlamydia trachomatis was previously shown to express a lipoprotein, the macrophage infectivity potentiator (Mip), exposed at the bacterial surface, and able to stimulate human primary monocytes/macrophages through Toll Like Receptor (TLR)2/TLR1/TLR6, and CD14. In PMA-differentiated THP-1 cells the proinflammatory activity of Mip was significantly higher in the absence than in the presence of serum. The present study aims to investigate the ability of different serum factors to attenuate Mip proinflammatory activity in PMA-differentiated THP-1 cells and in primary human differentiated macrophages.

Chlamydia trachomatis heat shock proteins 60 and 10 induce apoptosis in endocervical epithelial cells.

Aim And Objective: The potential role of chlamydial heat shock proteins (cHSP) 60 and cHSP10 in apoptosis of primary cervical epithelial cells was investigated.

Methods: Primary cervical epithelial cells were stimulated with cHSP60 and cHSP10 for 4 h. Quantitative measurements of apoptosis were made using cytofluorometry, and apoptosis-related genes were analyzed by microarray, real-time PCR and western blotting.

Anti-apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumatoid arthritis.

Objective: To determine whether anti-apolipoprotein A-1 (anti-Apo A-1) IgG are associated with major cardiovascular events in patients with rheumatoid arthritis (RA).

Methods: We determined anti-Apo A-1 IgG levels and the concentrations of cytokines, oxidized low-density lipoprotein (LDL), and matrix metalloproteinase 1 (MMP-1) MMP-2, MMP-3, and MMP-9 in sera from 133 patients with RA who did not have cardiovascular disease at baseline, all of whom were longitudinally followed up over a median period of 9 years. A major cardiovascular event was defined as a fatal or nonfatal stroke or acute coronary syndrome.

Influence of anti-infliximab antibodies and residual infliximab concentrations on the occurrence of acquired drug resistance to infliximab in rheumatoid arthritis patients.

Background: Infliximab (IFX) can be immunogenic for humans and lead to the formation of antibodies against IFX (anti-IFX Ab), which could induce acquired IFX resistance.

Objective: To test whether the presence of anti-IFX Ab and residual circulating IFX levels are associated with acquired IFX resistance in RA.

Methods: A multivariate logistic regression was used to analyze the relationship between anti-IFX Ab, residual IFX concentrations, and acquired IFX resistance in a nested cohort within the Swiss RA registry (SCQM-RA).

Diagnostic value of anti-cyclic citrullinated peptides and association with HLA-DRB1 shared epitope alleles in African rheumatoid arthritis patients.

Introduction: The purpose of this study was to examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA).

Methods: Serum levels of anti-cyclic citrullinated peptides antibodies (anti-CCP2, anti-CCP3), IgM and IgA rheumatoid factors (RF) were measured by enzyme-linked immunosorbent assay in the serum of 56 consecutive RA patients regularly followed in the Rheumatology Unit of the School of Medicine, University of Yaoundé, Yaoundé, Cameroon. Genotyping of HLA-DRB1 alleles was performed by polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes on microbeads arrays.

Cervical epithelial cells from Chlamydia trachomatis-infected sites coexpress higher levels of chlamydial heat shock proteins 60 and 10 in infertile women than in fertile women.

Background/aims: The objective of the present study was to examine the possible relationship between the chlamydial heat shock proteins (cHSP) 60 and 10 expression and the damaging sequelae of a Chlamydia trachomatis infection, such as infertility.

Methods: Seven fertile and 7 infertile female patients infected with C. trachomatis attending the gynecology outpatient department of Safdarjung hospital (New Delhi, India) were enrolled.

In infertile women, cells from Chlamydia trachomatis infected sites release higher levels of interferon-gamma, interleukin-10 and tumor necrosis factor-alpha upon heat-shock-protein stimulation than fertile women.

Background: The magnitude of reproductive morbidity associated with sexually transmitted Chlamydia trachomatis infection is enormous. Association of antibodies to chlamydial heat shock proteins (cHSP) 60 and 10 with various disease sequelae such as infertility or ectopic pregnancy has been reported. Cell-mediated immunity is essential in resolution and in protection to Chlamydia as well as is involved in the immunopathogenesis of chlamydial diseases.

The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14.

Chlamydiae components and signaling pathway(s) responsible for the production of proinflammatory cytokines by human monocytes/macrophages are not clearly identified. To this aim, Chlamydia trachomatis-inactivated elementary bodies (EB) as well as the following seven individual Ags were tested for their ability to induce the production of proinflammatory cytokines by human monocytes/macrophages and THP-1 cells: purified LPS, recombinant heat shock protein (rhsp)70, rhsp60, rhsp10, recombinant polypeptide encoded by open reading frame 3 of the plasmid (rpgp3), recombinant macrophage infectivity potentiator (rMip), and recombinant outer membrane protein 2 (rOmp2). Aside from EB, rMip displayed the highest ability to induce release of IL-1beta, TNF-alpha, IL-6, and IL-8.

Molecular characterization and subcellular localization of macrophage infectivity potentiator, a Chlamydia trachomatis lipoprotein.

Macrophage infectivity potentiator (MIP) was originally reported to be a chlamydial lipoprotein from experiments showing incorporation of radiolabeled palmitic acid into native and recombinant MIP; inhibition of posttranslational processing of recombinant MIP by globomycin, known to inhibit signal peptidase II; and solubility of native MIP in Triton X-114. However, the detailed structural characterization of the lipid moiety on MIP has never been fully elucidated. In this study, bioinformatics and mass spectrometry analysis, as well as radiolabeling and immunochemical experiments, were conducted to further characterize MIP structure and subcellular localization.

The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes.

Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8.

CD14 is an acute-phase protein.

The origin of soluble CD14 (sCD14) in the circulation is uncertain. To examine whether CD14 could be an acute-phase protein (APP), the levels of sCD14, IL-6, and C-reactive protein were determined by ELISA in serum and synovial fluid (SF) of patients with various arthropathies, and the regulation of CD14 synthesis was examined in liver cells. In patients with crystal-mediated or immunologically mediated arthritis (rheumatoid arthritis), serum levels of sCD14 were higher than or similar to those found in infection-mediated arthritis (reactive arthritis), precluding a relation with bacteria exposure.