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Objective: Anti–histidyl‐transfer RNA synthetase (Jo‐1) antibodies are associated with myositis as well as different extramuscular organ complications comprising the anti‐synthetase syndrome. This study aimed to clarify the relationship between anti–Jo‐1 epitope recognition patterns and specific clinical features of this syndrome. Methods: B cell epitope mapping was performed via enzyme‐linked immunosorbent assay in 180 patients who were anti–Jo‐1 antibody‐positive using overlapping peptides/protein fragments spanning the amino‐terminal 151 amino acids of Jo‐1 as substrate antigens. Statistical associations with clinical features were assessed through rank‐sum, correlation, and cluster analyses. Results: The level of reactivity against subfragments spanning amino acids 1–151 of Jo‐1 paralleled that of full‐length Jo‐1, confirming the immunodominance of this amino‐terminal region. The corresponding frequencies of reactivity to peptides 1 (amino acids [aa] 1–21), 3 (aa 27–47), 4 (aa 40–60), 10 (aa 118–138), and 11 (aa 131–151) were 6.1%, 42.5%, 6.8%, 6.7%, and 20.3%. While anti–full‐length Jo‐1 antibodies were significantly associated with Raynaud phenomenon, anti‐fragment A2 (aa 1–60) and A3 (aa 1–90) antibodies were associated with proximal muscle weakness, Raynaud phenomenon, arthritis, and sicca syndrome. Anti‐fragment A4 (aa 1–120) and A5 (aa 1–151) antibodies were also associated with sicca syndrome. Peptide 1 (aa 1–21) antibodies were associated with Raynaud phenomenon and dysphagia. Whereas anti‐peptide 3 (aa 27–47) antibodies were also linked to Raynaud phenomenon, anti‐peptide 9 (aa 105–125) antibodies were associated with mechanic's hands. Conclusion: Autoantibodies targeting different amino‐terminal subfragments and/or peptides of Jo‐1 were associated with specific clinical features of the anti‐synthetase syndrome, demonstrating the biomarker potential of B cell epitope profiling in this disorder. [ABSTRACT FROM AUTHOR]

Objectives Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (MDA5+) dermatomyositis patients exhibit a variety of clinical features. We therefore investigated whether patterns of B-cell epitope recognition are linked to the clinical course of MDA5+ dermatomyositis. Methods Our cross-sectional study used ELISA-based methods to determine the relationship between antibody recognition of overlapping 155 amino acid MDA5 subfragments and clinical features of 24 MDA5+ myositis patients. Correlations between clinical features and standardized anti-MDA5 subfragment antibody titres were assessed via Spearman's rank correlation coefficients. Results Twenty-four MDA5+ patients submitted serum samples within a median of 0 (interquartile range, 0–74) days from the initial clinic visit. In addition to typical dermatomyositis rashes, these patients exhibited muscle symptoms (n  = 11), vascular dysfunction (n  = 9) and interstitial lung disease (ILD) (n  = 16). Female patients exhibited higher titres of antibodies recognizing fragment H (aa 905–1026) compared with male patients. Muscle involvement was associated with higher levels of anti-fragment F (aa 646–801) antibody. Conversely, patients with vascular abnormalities had higher anti-fragment B (aa 130–284) and E (aa 517–671) antibody titres than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1–155) antibody titres than the other 20 patients. Differences in the ratio of anti-fragment to anti-full-length MDA5 antibody titres were found for sex (H: anti-MDA5) and vascular dysfunction (anti-fragment B, E: anti-MDA5). Conclusions Various clinical features of MDA5+ dermatomyositis correlated with levels of antibodies targeting selected subfragments of this autoantigen, providing a link between fragment-specific immune responses and disease course. [ABSTRACT FROM AUTHOR]