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

Koichi Yamaguchi; Paul Poland; Tissa Bijoy George; Didem Saygin; Siamak Moghadam-Kia; Rohit Aggarwal; Chester V Oddis; Lei Zhu; Dana P Ascherman

doi:10.1093/rheumatology/kead550

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

Rheumatology (Oxford). 2023 Oct 10:kead550. doi: 10.1093/rheumatology/kead550. Online ahead of print.

Authors

Koichi Yamaguchi^{1

2}, Paul Poland², Tissa Bijoy George², Didem Saygin², Siamak Moghadam-Kia², Rohit Aggarwal², Chester V Oddis², Lei Zhu², Dana P Ascherman²

Affiliations

¹ Department of Allergy and Respiratory Medicine, Gunma University Graduate School of Medicine, Gunma, Japan.
² Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

PMID: 37815819
DOI: 10.1093/rheumatology/kead550

Abstract

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 titers 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 titers of antibodies recognizing fragment H (aa 905-1026) compared to 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 titers than those without vascular dysfunction. Four patients died due to ILD progression and showed higher anti-fragment A (aa 1-155) antibody titers than the other 20 patients. Differences in the ratio of anti-fragment to anti-full length MDA5 antibody titers 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.

Keywords: anti-melanoma differentiation-associated gene 5 antibody; epitope; fragment; myositis.