Multiplex Analysis of Cerebrospinal Fluid and Serum Exosomes MicroRNAs of Untreated Relapsing Remitting Multiple Sclerosis (RRMS) and Proposing Noninvasive Diagnostic Biomarkers.

Abstract

Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for neurodegenerative diseases. In this study, we aimed to detect relapsing-remitting multiple sclerosis (RRMS)-specific miRNAs in cerebrospinal fluid (CSF) and serum exosomes with diagnostic potential. One ml of CSF and serum sample were collected from each of the 30 untreated RRMS patients and healthy controls (HCs). A panel of 18 miRNAs affecting inflammatory responses was applied, and qRT-PCR was conducted to detect differentially expressed exosomal miRNAs in CSF and serum of RRMS patients. We identified that 17 out of 18 miRNAs displayed different patterns in RRMS patients compared to HCs. Let-7 g-5p, miR-18a-5p, miR-145-5p, and miR-374a-5p with dual pro-inflammatory and anti-inflammatory actions and miR-150-5p and miR-342-3p with anti-inflammatory action were significantly upregulated in both CSF and serum-derived exosomes of RRMS patients compared to corresponding HCs. Additionally, anti-inflammatory miR-132-5p and pro-inflammatory miR-320a-5p were significantly downregulated in both CSF and serum-derived exosomes of RRMS patients compared to HCs. Ten of 18 miRNAs were differentially expressed in CSF and serum exosomes of the patients. Furthermore, miR-15a-5p, miR-19b-3p, and miR-432-5p were upregulated, and miR-17-5p was downregulated only in CSF exosomes. Interestingly, U6 housekeeping gene was differentially expressed in CSF and serum exosomes, in both RRMS and HCs. As the first report describing CSF exosomal miRNAs expression profile compared to that of serum exosomes in untreated RRMS patients, we showed that CSF and serum exosomes are not identical in terms of biological compounds and display different patterns in miRNAs and U6 expression.