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Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a better understanding of treatment effects
Journal
Clinical immunology
Volume
144
Number
1
Pages / Article-Number
70-9
Keywords
MicroRNA, Multiple sclerosis, B lymphocytes, Natalizumab, Expression
Abstract
MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. We compared the expression of 1059 miRNAs in B lymphocytes from untreated and natalizumab treated relapsing-remitting multiple sclerosis (RRMS) patients and healthy volunteers (HV). Forty nine miRNAs were down-regulated in untreated MS patients compared with HV. A distinct pattern of 10 differentially expressed miRNAs was found in natalizumab treated patients compared with untreated patients. Two clusters, i.e. miR-106b-25 and miR-17-92, were particularly deregulated. MiRNA-mRNA interaction analysis revealed B cell receptor, phosphatidyl-inositol-3-kinase (PI3K) and phosphatase and tensin homology (PTEN) signaling being the key affected pathways. We discovered deregulated viral miRNAs in untreated patients as compared with HV and natalizumab treated patients, a novel finding that may be related to latency and activation of viruses in MS. Our findings provide first insights into miRNA dependent regulation of B cell function in MS and the impact of a therapy not primarily targeting B cells on this regulation.
