Correlation between B-cell epitope profile and clinical features of anti-MDA5 antibody-positive dermatomyositis

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.