Differential Expression of Serum Extracellular Vesicle miRNAs in Multiple Sclerosis: Disease-Stage Specificity and Relevance to Pathophysiology

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Its first clinical presentation (clinically isolated syndrome, CIS) is often followed by the development of relapsing-remitting MS (RRMS). The periphery-to-CNS transmission of inflammatory molecules is a major pathophysiological pathway in MS. This could include signalling via extracellular vesicle (EV) microRNAs (miRNAs). In this study, we investigated the serum EV miRNome in CIS and RRMS patients and matched controls, with the aims to identify MS stage-specific differentially expressed miRNAs and investigate their biomarker potential and pathophysiological relevance. miRNA sequencing was conducted on serum EVs from CIS-remission, RRMS-relapse, and viral inflammatory CNS disorder patients, as well as from healthy and hospitalized controls. Differential expression analysis was conducted, followed by predictive power and target-pathway analysis. A moderate number of dysregulated serum EV miRNAs were identified in CIS-remission and RRMS-relapse patients, especially relative to healthy controls. Some of these miRNAs were also differentially expressed between the two MS stages and had biomarker potential for patient-control and CIS-RRMS separations. For the mRNA targets of the RRMS-relapse-specific EV miRNAs, biological processes inherent to MS pathophysiology were identified using in silico analysis. Study findings demonstrate that specific serum EV miRNAs have MS stage-specific biomarker potential and contribute to the identification of potential targets for novel, efficacious therapies.

Automated summary

This study investigated the serum extracellular vesicle (EV) microRNAs (miRNAs) in different stages of multiple sclerosis (MS) patients and matched controls, aiming to identify MS stage-specific differential expressed miRNAs and their potential as biomarkers and relevance to the disease. The study found a moderate number of dysregulated serum EV miRNAs in CIS-remission and RRMS-relapse patients, with some miRNAs having potential as biomarkers for patient-control and CIS-RRMS differentiation. In silico analysis identified biological processes related to MS pathophysiology as the mRNA targets of RRMS-relapse-specific EV miRNAs. The findings demonstrate the potential of specific serum EV miRNAs as MS stage-specific biomarkers and provide insights into potential therapeutic targets.