Altered microRNA expression in B lymphocytes in multiple sclerosis: Towards a better understanding of treatment effects

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• 作者：Claudia Sievers^a ; Maria Meira^a ; Francine Hoffmann^a ; Paulo Fontoura^b ; Ludwig Kappos^a ; Raija L.P. Lindberg^a ; ^{Raija.lindberg@unibas.ch}
• 关键词：RRMS ; relapsing&ndash ; remitting multiple sclerosis ; HV ; healthy volunteer ; miRNA ; microRNA
• 刊名：Clinical Immunology
• 出版年：2012
• 期刊代码：95_15216616
• 类别：imm
• 出版时间：July, 2012
• 卷：144
• 期：1
• 页码：70-79
• 文件大小：674 K

摘要

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.