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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.

Analizar el riesgo de fractura calculado por FRAX® y la frecuencia de alto riesgo de fractura en la población general en España.

To evaluate the validity of different spondyloarthritis (SpA) features included in the Berlin diagnostic algorithm and the Assessment of SpondyloArthritis international Society (ASAS) classification criteria in an early SpA cohort. This was a longitudinal multicenter study including patients from the ESPeranza program cohort who were suspected to have SpA. Subjects were ≤45 years old, and SpA symptom duration was 3–24 months. Patients with axial SpA symptoms were selected and categorized according to diagnosis (yes/no) of axial SpA. Descriptive analysis was performed, and the sensitivity, specificity, predictive value, and likelihood ratio (LR) of each feature were calculated. Of 775 patients suspected to have SpA, 665 had predominantly axial symptoms and 516 of these patients were diagnosed with axial SpA. The most useful SpA features were sacroiliitis on magnetic resonance imaging (positive LR 6.6) or radiograph (positive LR 31.1) and peripheral arthritis (positive LR 8.9). The features with the lowest diagnostic utility were a family history of SpA (positive LR 1.5) and good response to nonsteroidal antiinflammatory drugs (positive LR 1.6). Inflammatory back pain (IBP; according to ASAS criteria) was described in only 27% of SpA patients, with a positive LR of 2.3. HLA–B27 positivity was present in 245 (48%), and the positive LR was 2.8. The diagnostic value of SpA features in patients with early axial SpA seems to be different than in patients with longstanding disease. Chronic back pain is better than IBP as an entry point to the diagnostic algorithm. Sacroiliitis on imaging is very important for early diagnosis, while the use of HLA–B27 status as a key factor is questionable.

To describe health‐related quality of life (HRQOL) and physical function in patients with early axial spondyloarthritis (SpA) and to assess their associations with disease activity and radiographic damage. This was a cross‐sectional study drawing upon baseline data of axial SpA patients (Assessment of SpondyloArthritis international Society criteria) from the ESPERANZA cohort. Linear regression analyses were used to evaluate the associations between disease activity and radiographic damage (spine and sacroiliac joints) with HRQOL, physical function, and spinal mobility. In total, 259 patients were included. The mean ± SD age was 32.2 ± 6.9 years, disease duration was 13.3 ± 6.8 months, Ankylosing Spondylitis Quality of Life score was 5.9 ± 4.8, Bath Ankylosing Spondylitis Functional Index score was 2.4 ± 2.3, Bath Ankylosing Spondylitis Metrology Index score was 1.4 ± 1.3, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was 3.8 ± 2.3, C‐reactive protein (CRP) level was 9.7 ± 13.2 mg/liter, and Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI‐s) score was 1.7 ± 1.6. HRQOL was mainly associated with disease activity on univariate analysis (β values for BASDAI 0.646, patient global visual analog scale [VAS] 0.641, night back pain VAS 0.598, physician VAS 0.560, and CRP level 0.275; P< 0.01 for all), whereas the association with radiographic damage was weaker (standardized β for BASRI‐s 0.142; P< 0.05). On multivariate models, HRQOL only remained significantly associated with disease activity (standardized β for BASDAI 0.330; P< 0.01, and physician VAS 0.205 and night back pain VAS 0.210; P= 0.01). Similarly, physical function was associated with disease activity and radiographic damage on univariate analysis, but only with disease activity (BASDAI β 0.466; P< 0.01) on multivariate analysis. However, spinal mobility was associated with radiographic damage in both univariate and multivariate analyses. Patients with axial SpA already have impaired quality of life and physical function, albeit mildly, at the beginning of their disease course. Both outcomes are mainly associated with disease activity in these patients.

Objective: To evaluate the main outcomes of disease activity and their association with other measures of activity, damage, and quality of life in patients with idiopathic inflammatory myopathy (IIM) according to time since diagnosis and positivity to antisynthetase autoantibodies (ASAs). Methods: Cross-sectional multicenter study within the Spanish Myo-Spain registry. Cases were classified as incident (≤ 12 months since diagnosis) and prevalent. The main outcomes of disease activity were the Myositis Disease Activity Assessment visual analogue scale (MYOACT), the Manual Muscle Test 8 (MMT-8), physician global activity (PhGA), and extramuscular activity. Other measures of activity, damage, and quality of life included patient global disease activity, MYOACT muscular, creatine phosphokinase, Health Assessment Questionnaire, physician and patient global damage, global damage of the Myositis Damage Index, and the 12-item Short-Form Health Survey (SF-12). We analyzed associations using a multivariate generalized linear model and a simple linear regression model. Results: A total of 554 patients with different diagnostic subgroups of IIM were included (136 incident and 418 prevalent cases), with 215 ASA-positive patients (58 incident and 157 prevalent cases). All measures of disease activity were higher in the incident cases (p&lt; 0.05), except for MYOACT muscular and creatine phosphokinase, for which no differences were recorded in ASA-positive patients. No differences were found between incident and prevalent cases for measures of damage. Values for the physical component of the SF-12 were higher in the prevalent cases (p&lt; 0.05). The multivariate model was initially significant overall for the main activity outcomes. Positivity to ASAs was positively and negatively associated with the MYOACT index and MMT-8, respectively (p&lt; 0.05), although no association was recorded with PhGA and extramuscular activity. Prevalent cases were negatively associated with the main outcomes of activity, except with MMT-8, for which the association was positive (p&lt; 0.05). Conclusions: The main activity outcomes validated in polymyositis and dermatomyositis could also be used in other subtypes of IIM, such as antisynthetase syndrome. Recent diagnosis is associated with greater disease activity, as assessed based on these activity outcomes. PhGA and extramuscular activity are not modified by ASA positivity, thus supporting their preferred use for assessing treatment response in IIM with ASAs.