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 work

Correspondence: 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.com

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.

Keywords: Anti-MDA5 dermatomyositis, rapidly progressive interstitial lung disease, prognostic biomarkers, KL-6, transcriptomics, immunopathogenesis