Early response in cytokine and miR-124a, -125b, -223 expression to anti-CD20 in Multiple Sclerosis and its animal model - a preliminary analysis.

Abstract

INTRODUCTION: Multiple Sclerosis (MS) is an autoimmune, demyelinating, inflammatory disorder. The anti-CD20 monoclonal antibody ocrelizumab targets B cells, effectively controlling the disease. MicroRNAs (miRNAs), small molecules modulating immune responses and neuroinflammation, may serve as biomarkers for disease progression, though the impact of anti-CD20 remains unclear. We hereby selected three miRNAs of interest for their relevance in experimental autoimmune encephalomyelitis (EAE) and MS, miR-124a-3p, miR-125b-5p, and miR-223-3p. METHODS: We examined these miRNAs in the spinal cord of EAE mice treated with a nanoformulation of anti-CD20 and in 23 MS patients' serum (19 relapsing-remitting [RR] and 4 primary-progressive [PP]) before (T0) and after six months (T6) of ocrelizumab, alongside with serum cytokines and chemokines. RESULTS: We found reduced (*p = 0.045) miR-223-3p in nano-anti-CD20-treated mice and in patients (*p = 0.030) with inactive MS. RRMS showed varying miRNA expression, while PPMS exhibited reduced (*p = 0.029) miR-124a-3p at T6. CXCL10 was elevated (*p = 0.024) in patients with active MS. Overall, six cytokines increased at T6, with interleukin 6 (IL6) negatively correlating with miR-223-3p. Gene analysis showed that IL6 gene is among miRNAs' targets, alongside inflammatory pathways. CONCLUSIONS: This is the first study to compare miR-124a-3p, miR-125b-5p, and miR-223-3p in both EAE and MS patients undergoing anti-CD20 therapy, suggesting subtype-specific molecular responses, identifying miR-223-3p as a potential biomarker of treatment response, and highlighting immune regulatory pathways as key mechanisms linking these miRNAs to disease progression and therapy outcomes.