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. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

Prevalence of Sjögren's syndrome in the general adult population in Spain: estimating the proportion of undiagnosed cases.

To estimate the prevalence of Sjögren's syndrome (SS) in the adult Spanish population we performed a population-based multicenter cross-sectional study. Cases were defined by the American-European Consensus Group criteria proposed in 2002. A total of 4,916 subjects aged 20 years or over were included. The estimated prevalence of SS (including primary and secondary forms) in the adult population in Spain was 0.33% (95% CI 0.21-0.53). Extrapolating to the total population of the country aged ≥ 20 years (around 37.7 million persons), there would be around 125,000 cases of SS in Spain. Considering only primary SS, the estimated prevalence was 0.25% (95% CI 0.15-0.43) or 1 person in 400. The prevalence of primary SS in Spain is comparable to that reported in other European studies with a similar design and diagnostic criteria. Based on these results, primary SS could not be considered a rare (orphan) disease. Only 50% of cases had already been diagnosed with SS prior EPISER 2016 study, confirming the existence of a non-negligible proportion of undiagnosed cases in the general population.

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. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Prevalence of rheumatic diseases in adult population in Spain (EPISER 2016 study): Aims and methodology. / Prevalencia de enfermedades reumáticas en población adulta en España (estudio EPISER 2016). Objetivos y metodología.

AIMS: To describe the methodology of the EPISER 2016 (study of the prevalence of rheumatic diseases in adult population in Spain), as well its strengths and limitations. The aim of this study is to estimate the prevalence of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), osteoarthritis (knee, hip, hands, and cervical and lumbar spine), fibromyalgia, gout and clinical osteoporotic fracture. MATERIAL AND METHOD: Population-based, multicenter, cross-sectional study, with the participation of 45 municipalities in the 17 Spanish autonomous communities. The reference population will consist of adults aged 20 years and over residing in Spain. A computer-assisted telephone interview (CATI) system will be used for data collection. Diagnostic suspicions and diagnoses received by the participants will be studied by rheumatologists in the referral hospitals in the selected municipalities. STATISTICAL ANALYSIS: the prevalence of the rheumatic diseases will be calculated using estimators and their 95% confidence intervals. Weights will be calculated in each of the sampling stages in accordance with the probability of selection. The distribution of the population in Spain will be obtained from the Spanish Statistics Institute. CONCLUSIONS: Sociodemographic and lifestyle changes over the last 16 years justify EPISER 2016. This study will provide current data about the prevalences of RA, AS, PsA, SLE, SS, osteoarthritis, fibromyalgia, gout and clinical osteoporotic fracture. The results will allow comparisons with studies from other countries and EPISER 2000.

Efficacy of rituximab in dermatomyositis and polymyositis refractory to conventional therapy.

We report one case of dermatomyositis and one of polymyositis refractory to several conventional inmunosupressive therapies, which present a response after treatment with rituximab, enabling steroid dose reduction and a prolonged remission.