Baseline miR-10a, miR-146a, and miR-155 expression and subsequent clinical and radiological outcomes in multiple...

Multiple sclerosis (MS) is a chronic, immune-mediated central nervous system disorder with a multifactorial etiology, driven by genetic-environmental interplay. MicroRNAs (miRNAs), small non-coding RNAs, act as key post-transcriptional regulators within epigenetic mechanisms, integrating these determinants into gene expression networks. Increasing evidence implicates miRNA dysregulation as an important contributor to MS pathogenesis and progression. Between 2015 and 2018, expression levels of miR-10a, miR-146a, and miR-155 were obtained from whole blood samples of patients with MS using RT-PCR and evaluated to investigate associations between baseline miRNA expression patterns and subsequent clinical and radiological outcomes. Based on these data, the medical records of 54 patients who remained under follow-up (2015-2023) were reviewed retrospectively. Following expression analysis, the number of relapses, annualized relapse rate, changes in Expanded Disability Status Scale (EDSS) score, radiological activity, and achievement of No Evidence of Disease Activity (NEDA-3) status were assessed over a mean follow-up period of approximately 5 years. A total of 54 patients (40 female and 14 male) were included. The mean follow-up period was 62.44 ± 21.14 months (14-81 months). The median age at diagnosis was 31 years (16-53 years). Differences in miR-10a expression levels were found in 37 patients (68.5%), miR-146a in 36 (66.7%), and miR-155 in 41 (75.9%). miR-10a dysregulation was significantly associated with the final EDSS score (P = .007) and the presence of cervical spinal cord lesions at baseline (P = .040). miR-146a and miR-155 dysregulation were significantly associated with the development of new cervical spinal cord lesions (P = .020 and P = .025, respectively). miR-155 also showed a nominal association with overall radiological activity (P = .049). Exploratory ROC analysis showed limited discriminatory performance of miR-155 for radiological activity (AUC = 0.655, 95% CI: 0.513-0.779; P = .0387). In this exploratory retrospective study, baseline expression patterns of miR-10a, miR-146a, and miR-155 were associated with selected subsequent clinical and radiological outcomes in patients with MS. Associations were observed between miR-10a and disability measures, between miR-146a/miR-155 and new cervical spinal cord lesions, and between miR-155 and radiological activity. These findings should be considered hypothesis-generating and require confirmation in larger prospective studies with longitudinal miRNA assessment and independent validation.