Background: Inflamma-miRs are a group of microRNAs involved in the regulation of innate and adaptive immune responses. Increasing evidence support the contribution of dysregulated inflamma-miRs in the pathogenesis of multiple sclerosis. The aim of this study was to evaluate the expression of selected inflamma-miRs, i.e., miR-34a-5p, -125a-5p, -146a-5p, and -155, in relapsing-remitting multiple sclerosis (RRMS) and their modulation after treatment with dimethyl fumarate (DMF).

Methods: Circulating levels of microRNAs involved in inflammatory response (inflamma-miRs) were compared between healthy controls (CTRs, n=21) and patients with RRMS (n=24) who started treatment with DMF.

Results: Plasma levels of miR-34a (p<0.001) and miR-125a-5p (p=0.034) were higher, whereas miR-146a-5p levels were lower (p=0.041) in RRMS patients compared to CTRs. Circulating miR-125a-5p (p=0.001), miR-146a-5p (p<0.001), and miR-155 (p=0.013) were reduced after 4-month treatment with DMF. Among these, baseline and 4-month follow up miR-125a-5p (p=0.028) and miR-146a-5p (p=0.042) levels were related to disability progression.

Conclusions: Circulating inflamma-miRs could represent candidate tools to predict MS clinical course and evaluate the effectiveness of disease-modifying treatments in RRMS.