Differential Modulation of MicroRNAs (miRNAs) in Patients With Systemic Sclerosis-Associated Skeletal Muscle Loss

Objective: This study aims to evaluate the differential expression of selected microRNAs (miRNAs) in patients with systemic sclerosis and investigate their association with skeletal muscle loss.Methodology: This retrospective observational study reviewed the medical records of patients with systemic sclerosis treated at a tertiary care teaching hospital between January 2024 and December 2024.Age-and sex-matched healthy individuals served as controls.Clinical data, skeletal muscle index (SMI), and handgrip strength were obtained from medical records.At the same time, archived serum samples were analyzed for the expression of selected miRNAs (miR-21, miR-29, miR-133a, and miR-206) using quantitative real-time polymerase chain reaction.Comparative analyses were performed between patients with and without skeletal muscle loss and between patients and healthy controls.Correlation and receiver operating characteristic curve analyses were conducted to evaluate the association and diagnostic performance of miRNAs.Results: A total of 110 participants were included, comprising 70 patients with systemic sclerosis and 40 healthy controls.Patients with systemic sclerosis demonstrated significant dysregulation of miRNA expression compared with healthy controls.Profibrotic miR-21 and muscle-associated miR-206 were significantly upregulated, whereas antifibrotic miR-29 and muscle-regulatory miR-133a were significantly downregulated, particularly among patients with skeletal muscle loss.Altered miRNA expression showed significant correlations with reduced SMI and handgrip strength.The miRNAs showed moderate discriminatory ability for prevalent skeletal muscle loss in this sample.Conclusion: Differential modulation of miRNAs is significantly associated with skeletal muscle loss in systemic sclerosis.These findings suggest that selected miRNAs may serve as promising noninvasive biomarkers for early detection and monitoring of muscle involvement and may represent potential therapeutic targets for preventing muscle wasting in systemic sclerosis.