Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a better understanding of treatment effects.
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.
Clinical Neuroimmunology, Department of Biomedicine and Neurology, University Hospital Basel, Switzerland.
Claudia
C
Sievers
Maria
M
Meira
Francine
F
Hoffmann
Paulo
P
Fontoura
Ludwig
L
Kappos
Raija L P
RL
Lindberg
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D000069442:Natalizumab
D061067:Antibodies, Monoclonal, Humanized; D035683:MicroRNAs; D000069442:Natalizumab