Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

Background: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA.

Results: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies.

Acroosteolysis and facial dysmorphia: a new case of Hajdu-Cheney syndrome.

Hajdu-Cheney syndrome or acro-dento-osteo-dysplasia syndrome is a rare disease characterized by band osteolysis of distal phalanges and facial dysmorphia, among other manifestations. We present the case of a 45-year-old male who consulted for mechanical joint pain of both hands, facial dysmorphism, cranio-facial alterations, and digital telescoping with acroosteolysis.

Humoral responses against HDL are linked to lipoprotein traits, atherosclerosis, inflammation and pathogenic pathways during early arthritis stages.

Objective: Chronic inflammation and immune dysregulation are crucial mechanisms for atherosclerosis in RA. Recent evidence suggests a link via humoral responses against high-density lipoproteins (HDL). This study aimed to characterize the specificity, clinical relevance and emergence of humoral responses against HDL along disease course, especially during the earliest phases of arthritis.

Experts document on methotrexate use in combined therapy with biological or targeted synthetic disease modifying drugs in patients with rheumatoid arthritis.

Objective: We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA).

Methods: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs.

Do NSAIDs Take Us Away From Treatment Goals in Axial Spondyloarthritis: A Story About Dysbiosis or Just a Matter of Bias?

Non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of treatment for spondyloarthritides (SpA), a group of entities with common clinical and pathophysiological aspects, but also with differential features. Although NSAIDs provide significant symptomatic relief, especially for joint pain and morning stiffness, their role in achieving and maintaining the treatment goals advocated by the treat to target strategy in SpA is not entirely clear. These agents can induce changes in the composition of the intestinal microbiota, also favoring an alteration of the barrier function in the gut epithelium.

Dietary habits in patients with fibromyalgia: a cross-sectional study.

Objectives: To the scarce information on dietary habits in fibromyalgia (FM), it is added that there are no comparative studies with other rheumatic diseases. The objective of this study was to characterise the dietary habits of patients with FM by comparing, for the first time, with healthy controls (HC) and rheumatoid arthritis (RA).

Methods: This cross-sectional, observational study was based on data obtained from the Dietfibrom project for FM and from the IMID Consortium for RA and HC.

Experts document on methotrexate use in combined therapy with biological or targeted synthetic disease modifying drugs in patients with rheumatoid arthritis.

Objective: We aimed to develop recommendations for the management of methotrexate (MTX) when considering the combination with biological (b) or targeted synthetic (ts) disease modifying drugs (DMARDs) in rheumatoid arthritis (RA).

Methods: Eleven experts on RA were selected. Two coordinators formulated 13 questions about the combination therapy of MTX with bDMARDs or tsDMARDs.

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis.

Objective: Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes.

GlycA Levels during the Earliest Stages of Rheumatoid Arthritis: Potential Use as a Biomarker of Subclinical Cardiovascular Disease.

This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early RA patients, 14 clinically-suspect arthralgia (CSA), and 28 controls. Serum glycosyltransferase activity was assessed by a colorimetric assay.

A Combined Transcriptomic and Genomic Analysis Identifies a Gene Signature Associated With the Response to Anti-TNF Therapy in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is the most frequent autoimmune disease involving the joints. Although anti-TNF therapies have proven effective in the management of RA, approximately one third of patients do not show a significant clinical response. The objective of this study was to identify new genetic variation associated with the clinical response to anti-TNF therapy in RA.

Vitamin D Receptor Polymorphism and DHCR7 Contribute to the Abnormal Interplay Between Vitamin D and Lipid Profile in Rheumatoid Arthritis.

Emerging evidence suggests a role for 7-dehydrocholesterol reductase (DHCR7) in the crosstalk between cholesterol and vitamin D. Our aim was to evaluate the impact of vitamin D-related polymorphisms and DHCR7 levels in the association between vitamin D deficiency and altered lipid profile in rheumatoid arthritis (RA). Serum 25(OH)-vitamin D, DHCR7 levels and vitamin D-related polymorphisms (VDR-rs2228570, CYP27A1-rs933994, CYP2R1-rs10741657 and DHCR7-rs12785878) were analyzed in 211 RA patients,94 controls and in a prospective cohort of 13 RA patients undergoing TNFα-blockade.

IRF4 and IRGs Delineate Clinically Relevant Gene Expression Signatures in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Overactivation of the type I interferon (IFN) signature has been observed in several systemic autoimmune conditions, such as Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA). Impaired control of Interferon-Responding Genes (IRGs) expression by their regulatory mechanisms, including Interferon Regulatory Factors (IRFs), may underlie these findings and it may explain the heterogeneity observed among these conditions. In the present study we aimed to evaluate the associations between IRF4 gene expression and those of IRGs in SLE and RA patients to gain insight about its links with the IFN signature as well as to explore the potential clinical relevance of these associations.

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

Objective: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.

Profiling of B-Cell Factors and Their Decoy Receptors in Rheumatoid Arthritis: Association With Clinical Features and Treatment Outcomes.

B-cell activation is pivotal in rheumatoid arthritis (RA) pathogenesis and represents a relevant therapeutic target. The main aim of this study was to characterize the profiles of B-cell factors and their decoy receptors in RA and evaluate their clinical relevance. sBLyS, sAPRIL, sBCMA, sTACI, sBLyS-R, and several cytokines' serum levels were measured by immunoassays in 104 RA patients and 33 healthy controls (HC).

Biological Dose Tapering in Daily Clinical Practice: A 10 Year Follow-up Study.

Objective: To describe practice patterns, long-term outcome, and related factors, in relation to biological therapies tapering in rheumatoid arthritis (RA) patients in a well-controlled real-world setting.

Methods: An observational longitudinal retrospective 10-year study was conducted in all RA patients receiving biological agents in an RA clinic from May 2003 to October 2013. Biological treatment of patients with sustained DAS28<3.

Identification of a 3'-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study.

Objective: To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA).

Methods: We performed a genome-wide association study (GWAS) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima-media thickness (CIMT) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals.

Heterogeneity of the Type I Interferon Signature in Rheumatoid Arthritis: A Potential Limitation for Its Use As a Clinical Biomarker.

Introduction: An increased expression of interferon (IFN)-responding genes (IRGs), the so-called IFN signature, has been reported in rheumatoid arthritis (RA). However, some controversy exists concerning its clinical relevance. The main aim of this study is to evaluate whether quantitative and qualitative differences in the activation of the IFN pathway may account for these findings.

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the spanish cohort of the COMORA study.

Objectives: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA).

Methods: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression.

High triglycerides and low high-density lipoprotein cholesterol lipid profile in rheumatoid arthritis: A potential link among inflammation, oxidative status, and dysfunctional high-density lipoprotein.

Background: The interactions between inflammation and lipid profile in rheumatoid arthritis (RA) are poorly understood. The lipid profile study in RA has been biased toward lipoprotein levels, whereas those of triglycerides (TGs) and lipoprotein functionality have been underestimated.

Objectives: Since recent findings suggest a role for TG and TG-rich lipoproteins (TRL) on inflammation, we aimed to evaluate a combined lipid profile characterized by high TG and low high-density lipoprotein cholesterol levels (TGHDL) in RA.

Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis.

Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of high-density lipoprotein (HDL) has been observed. Although the actual players are unknown, anti-HDLs were associated with altered lipid profile, decreased paraoxonase 1 (PON1) activity and CV disease in RA.

Non-Esterified Fatty Acids Profiling in Rheumatoid Arthritis: Associations with Clinical Features and Th1 Response.

Objectives: Since lipid compounds are known to modulate the function of CD4+ T-cells and macrophages, we hypothesize that altered levels of serum non-esterified fatty acids (NEFA) may underlie rheumatoid arthritis (RA) pathogenesis.

Methods: Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, γ-linoleic, arachidonic -AA-, linolenic, eicosapentaenoic -EPA- and docosahexaenoic -DHA-) were quantified by LC-MS/MS after methyl-tert-butylether (MTBE)-extraction in 124 RA patients and 56 healthy controls (HC). CD4+ phenotype was studied by flow cytometry.

A genome-wide association study identifies SLC8A3 as a susceptibility locus for ACPA-positive rheumatoid arthritis.

Objective: RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach.

Methods: A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase.

Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti-High-Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease.

Objective: Paraoxonase 1 (PON-1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme that plays an important role in HDL-mediated cardioprotection. Although genetic polymorphisms are known to modulate PON-1 activity, its involvement in cardiovascular disease (CVD) in rheumatoid arthritis (RA) is controversial, suggesting that other factors may modulate its function. Since anti-HDL antibodies have been found to be related to an impaired lipid profile and occurrence of CVD in RA, this study was undertaken to examine the associations between PON-1 activity, anti-HDL antibodies, and CVD according to PON1 genetic variants in patients with RA.

Identification of IRX1 as a Risk Locus for Rheumatoid Factor Positivity in Rheumatoid Arthritis in a Genome-Wide Association Study.

Objective: Rheumatoid factor (RF) is a well-established diagnostic and prognostic biomarker in rheumatoid arthritis (RA). However, ∼20% of RA patients are negative for this anti-IgG antibody. To date, only variation at the HLA-DRB1 gene has been associated with the presence of RF.