Circulating microRNA expression profiles as biomarkers of disease activity in multiple sclerosis

Background: Reliable biomarkers of inflammatory activity in multiple sclerosis (MS) are needed to complement clinical and MRI assessments. Circulating microRNAs (miRNAs) are promising candidates due to their serum stability and involvement in MS-related biological pathways. Objectives: To evaluate whether selected serum miRNAs can discriminate relapse from remission in treatment-naive patients with relapsing-remitting MS (RRMS). Methods: In this prospective paired study, newly diagnosed, untreated RRMS patients were sampled during clinical relapse and subsequent remission. A targeted miRNA panel was quantified using quantitative PCR. Differential expressions were assessed using paired statistical testing with multiple comparison correction. Diagnostic performance was evaluated using ROC analysis and multivariate logistic regression. Pathway enrichment analysis was performed using Ingenuity Pathway Analysis. Results: = 0.043). A three-miRNA panel (hsa-miR-122-5p, hsa-miR-15b-5p, hsa-miR-30e-5p) demonstrated high discriminative accuracy (area under the curve = 0.88; 95% CI 0.79-0.96). Pathway analysis highlighted inflammatory, metabolic, and hypoxia-related processes. Conclusions: Circulating miRNAs distinguished relapse from remission in treatment-naive RRMS patients, suggesting their potential as complementary biomarkers of disease activity. These findings should be considered exploratory and require validation in an independent, larger cohort.