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Background Interstitial lung disease due to rheumatoid arthritis (RA-ILD) affects a substantial minority of patients with RA, inducing life-altering symptoms, impairing quality of life (QOL) and forcing patients to confront the potential for shortened survival. Dyspnoea is the predominant respiratory symptom of RA-ILD and a strong driver of QOL impairment in patients with it. The D12 is a 12-item questionnaire that assesses the physical and affective components of dyspnoea. It was one of a battery of patient-reported outcomes used in the double-blind, placebo-controlled TRAIL 1 trial of pirfenidone for RA-ILD. There is little information on the reliability, validity or responsiveness of the D12 in RA-ILD.Methods In accordance with COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) methodology, we conducted analyses on data from the TRAIL 1 trial to assess the measurement properties of the D12.Results Internal consistency (α=0.95, 0.95, 0.95, 0.95 and 0.96 at baseline, 13, 26, 39 and 52 weeks) and test-retest reliability 0.85 (0.71 to 0.92) exceeded acceptability criteria. Well over the 75% benchmark of hypotheses (43/46=93%) around D12 measurement properties were confirmed. Known-groups validity was supported by significant differences between subgroups of patients with differing levels of dyspnoea (eg, St. George’s Respiratory Questionnaire (SGRQ) Activity score ≥50 vs

Objective Patients with anti‐melanoma‐differentiation‐associated 5 (anti‐MDA5)‐positive dermatomyositis (DM) share several striking similarities to patients with SARS‐CoV‐2. Our objective was to assess the prevalence of anti‐angiotensin converting enzyme‐2 (ACE2) immunoglobulin M (IgM) antibodies, found in patients with severe SARS‐CoV‐2, in two independent anti‐MDA5‐positive DM cohorts. Methods Anti‐ACE2 IgM antibodies were assayed by enzyme‐linked immunosorbent assay (ELISA) in two anti‐MDA5‐positive DM cohorts: a predominantly outpatient North American cohort (n = 52) and a Japanese cohort enriched for new‐onset disease (n = 32). Additionally, 118 patients with SARS‐CoV‐2 with a spectrum of clinical severity were tested for anti‐MDA5 antibodies by ELISA. Results Five of fifty‐two (9.6%) North American patients and five of thirty‐two (15%) Japanese patients were positive for anti‐ACE2 IgM. In the North American cohort, all five patients with anti‐ACE2 IgM antibodies had proximal muscle weakness, had interstitial lung disease, were significantly more likely to receive pulse dose methylprednisolone (80% vs 30%, P = 0.043), and had worse forced vital capacity (median 59% predicted vs 78%, P = 0.056) compared with the anti‐ACE2‐IgM‐negative group. In the Japanese cohort, all five anti‐ACE2‐IgM‐positive patients also required pulse dose methylprednisolone, and three of five (60%) patients died. Japanese patients with anti‐ACE2 IgM had significantly worse oxygenation, as defined by a lower partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (233 vs 390, P = 0.021), and a higher alveolar‐arterial oxygenation gradient (91 vs 23 mm Hg, P = 0.024) than the IgM‐negative group. Conclusion We describe anti‐ACE2 IgM autoantibodies in two independent cohorts with anti‐MDA5‐positive DM. These autoantibodies may be biomarkers for severe disease and provide insight into disease pathogenesis.

A subset of rheumatoid arthritis (RA) patients have detectable antibodies directed against the peptidyl-arginine deiminase (PAD) enzyme isoforms 3 and 4. Anti-PAD3/4 cross-reactive antibodies (anti-PAD3/4XR) have been shown to lower the calcium threshold required for PAD4 activation, an effect potentially relevant to the pathogenesis of RA-associated interstitial lung disease (ILD).RA patients underwent multi-detector computed tomography (MDCT) of the chest with interpretation by a pulmonary radiologist for ILD features. A semi-quantitative ILD Score (range 0-32) was calculated. Concurrent serum samples were assessed for antibodies against PAD by immunoprecipitation with radiolabeled PAD3 and PAD4.Among the 176 RA patients studied, any ILD was observed in 58 (33%) and anti-PAD3/4XR was detected in 19 (11%). The frequency of any ILD among those with anti-PAD3/4XR was 68% vs. 29% among those with no anti-PAD (crude OR = 5.39; p = 0.002) and vs. 27% among those with anti-PAD4 that was not cross-reactive with PAD3 (crude OR = 5.74; p = 0.001). Both associations were stronger after adjustment for relevant confounders (adjusted ORs = 7.22 and 6.61, respectively; both p-values

Objective: Patients with immune-mediated necrotizing myopathy (IMNM) often have autoantibodies recognizing the signal recognition particle (SRP) or HMG-CoA reductase (HMGCR). Here, we studied a cohort of anti-SRP patients to identify factors associated with disease severity and clinical improvement; we also compared the severity of weakness in those with anti-SRP versus anti-HMGCR autoantibodies., Methods: All anti-SRP patients in the Johns Hopkins Myositis Cohort from 2002 to 2015 were included. Longitudinal information regarding proximal muscle strength, creatine kinase (CK) levels, and immunosuppressive therapy was recorded at each visit. Univariate and multivariate multilevel regression models were used to assess prognostic factors influencing recovery. Strength in the anti-SRP patients was compared to strength in 49 previously described anti-HMGCR subjects., Results: Data from 37 anti-SRP patients and 380 total clinic visits were analyzed. Younger age at onset was associated with more severe weakness at the first visit (P = 0.02) and all subsequent visits (P = 0.002). Only 50% of patients reached near-full or full strength after 4 years of treatment, and most of these continued to have elevated CK levels. Rituximab appeared to be effective in 13 of 17 anti-SRP patients. Anti-SRP patients were significantly weaker than those with anti-HMGCR autoantibodies (-1.3 strength points; P = 0.001)., Conclusion: Younger age at onset is associated with more severe weakness in anti-SRP myositis. Furthermore, even among anti-SRP patients whose strength improved with immunosuppression, most had ongoing disease activity as demonstrated by elevated CK levels. Finally, anti-SRP patients were significantly weaker than anti-HMGCR patients, providing evidence that these autoantibodies are associated with distinct forms of IMNM., (© 2016, American College of Rheumatology.)