Ren Yunli, Wu Tianqi, Shi Weiwei
Department of Rheumatology and Immunology, Affiliated Hospital 2 of Nantong University, Nantong, People's Republic of China.
School of Medicine, Nantong University, Nantong, People's Republic of China.
Clin Cosmet Investig Dermatol. 2025 Aug 9;18:1917-1929. doi: 10.2147/CCID.S535704. eCollection 2025.
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.
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.
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.
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.
全面描述抗MDA5抗体阳性皮肌炎（MDA5-DM）的临床特征、诊断挑战和预后生物标志物，结合转录组分析以阐明潜在的分子机制。
我们对29例MDA5-DM患者进行了回顾性分析，收集详细的临床和实验室数据。使用LASSO回归确定预后因素，并通过Cox比例风险模型和Kaplan-Meier生存分析进行验证。分析公共转录组数据集（GSE143323）以识别差异表达基因和富集的免疫途径。
患者误诊率高（62.1%），间质性肺疾病普遍（96.6%），41.4%发生快速进展性ILD（RP-ILD）。血清KL-6水平成为死亡率的独立预测因子（HR=2.96，p<0.01）。转录组分析显示IL-17、Toll样受体和细胞因子受体相互作用途径上调。
MDA5-DM存在巨大的诊断挑战，误诊率高，且主要由RP-ILD导致的死亡风险大。血清KL-6是一种强大的、临床适用的预后生物标志物，值得纳入风险分层方案。转录组研究结果揭示了关键的免疫炎症级联反应，特别是细胞因子网络和IL-17信号传导，提供了机制见解和潜在的治疗靶点。未来多中心前瞻性研究对于验证这些生物标志物研究结果并开发纳入临床影像学和分子参数的综合预后模型至关重要。
