Treatment status influences circulating microRNA expression and their clinical and radiological associations in multiple sclerosis

Abstract Circulating microRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS) due to their involvement in the regulation of multiple disease-related pathways. The aim of this study was to evaluate the impact of treatment status on the expression of a selected miRNAs panel and to investigate their associations with clinical and radiological variables in patients with MS (pwMS). Cross-sectional study was conducted in pwMS. Clinical disability was measured with Expanded Disability Status Scale (EDSS), cognitive function using the Processing Speed Test (PST), and brain volumetry using NeuroQuant®. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) were quantified using Simoa®. MiRNAs were quantified by quantitative PCR following serum RNA extraction. Most analyzed miRNAs differed significantly between treated and untreated patients in both expression levels and variability. In treated patients, miR-9-5p was positively correlated with EDSS, whereas in untreated patients, miR-223-3p and miR-146a-5p were positively correlated with PST. Moreover, miR-9-5p was negatively associated, whereas miR-223-3p was positively associated with volumes of multiple brain regions. In addition, miR-126-3p discriminated between MS phenotypes. These findings support miR-9-5p, miR-223-3p, miR-146a-5p and miR-126-3p as candidate MS biomarkers and demonstrate that treatment status influences both their expression and their associations with clinical and radiological variables.