Clinical and Molecular Insights Into Anti-MDA5 Antibody-Positive Dermatomyositis: A Single-Center Retrospective and Transcriptomic Study

Yunli Ren,1,* Tianqi Wu,2,* Weiwei Shi3,4 1Department of Rheumatology and Immunology, Affiliated Hospital 2 of Nantong University, Nantong, People’s Republic of China; 2School of Medicine, Nantong University, Nantong, People’s Republic of China; 3Department of Dermatology, Af...

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Main Authors: Ren Y, Wu T, Shi W
Format: Article
Language:English
Published: Dove Medical Press 2025-08-01
Series:Clinical, Cosmetic and Investigational Dermatology
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Online Access:https://www.dovepress.com/clinical-and-molecular-insights-into-anti-mda5-antibody-positive-derma-peer-reviewed-fulltext-article-CCID
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Summary:Yunli Ren,1,* Tianqi Wu,2,* Weiwei Shi3,4 1Department of Rheumatology and Immunology, Affiliated Hospital 2 of Nantong University, Nantong, People’s Republic of China; 2School of Medicine, Nantong University, Nantong, People’s Republic of China; 3Department of Dermatology, Affiliated Hospital 2 of Nantong University, Nantong, People’s Republic of China; 4Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiwei Shi, Department of Dermatology, Affiliated Hospital 2 of Nantong University, No. 666,Shengli Road, Nantong, 226000, People’s Republic of China, Email youzhi_gg@126.comObjective: To comprehensively characterize clinical features, diagnostic challenges, and prognostic biomarkers of anti-MDA5 antibody-positive dermatomyositis (MDA5-DM), incorporating transcriptomic analysis to elucidate underlying molecular mechanisms.Methods: We conducted a retrospective analysis of 29 MDA5-DM patients, collecting detailed clinical and laboratory data. Prognostic factors were identified using LASSO regression, validated by Cox proportional hazards and Kaplan-Meier survival analyses. Public transcriptomic dataset (GSE143323) was analyzed to identify differentially expressed genes and enriched immune pathways.Results: Patients exhibited a high misdiagnosis rate (62.1%) and prevalent interstitial lung disease (96.6%), with 41.4% developing rapidly progressive ILD (RP-ILD). Serum KL-6 level emerged as an independent predictor of mortality (HR=2.96, p< 0.01). Transcriptomic profiling revealed upregulation of IL-17, Toll-like receptor, and cytokine–receptor interaction pathways.Conclusion: MDA5-DM presents formidable diagnostic challenges with high misdiagnosis rates and substantial mortality risk predominantly driven by RP-ILD. Serum KL-6 represents a robust, clinically applicable prognostic biomarker warranting integration into risk stratification protocols. Transcriptomic findings illuminate critical immune-inflammatory cascades, particularly cytokine networks and IL-17 signaling, offering mechanistic insights and potential therapeutic targets. Future multicenter prospective studies are essential to validate these biomarker findings and develop composite prognostic models incorporating clinical, radiographic, and molecular parameters.Keywords: Anti-MDA5 dermatomyositis, rapidly progressive interstitial lung disease, prognostic biomarkers, KL-6, transcriptomics, immunopathogenesis
ISSN:1178-7015