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

Abstract

Objective: 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.