MiR-126: a novel route for natalizumab action?

Meira, Maria and Sievers, Claudia and Hoffmann, Francine and Derfuss, Tobias and Kuhle, Jens and Kappos, Ludwig and Lindberg, Raija L. P.. (2014) MiR-126: a novel route for natalizumab action? Multiple Sclerosis Journal, 20 (10). pp. 1363-1370.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61688/

Downloads: Statistics Overview


MicroRNAs (miRNAs) have emerged as a family of post-transcriptional regulators of gene expression that mediate diverse aspects of immunity. MiRNA dysregulation has been found in multiple sclerosis (MS), reflecting the growing need to identify disease-specific miRNA expression signatures. Our previous low-density array studies reveal differential miR-126 expression in the CD4(+)T cells of untreated relapsing-remitting MS (RRMS) patients. Here, we investigated miR-126 expression in natalizumab-treated patients. We isolated CD4(+) T cells from untreated (n = 12) and natalizumab-treated MS patients (n = 24), and from healthy volunteers (n = 12). We analyzed the expression of miRNAs and potential targets by real time reverse transcription polymerase chain reaction (RT-PCR). We assessed specific inhibition of miR-126, in vitro. MiR-126 was down-regulated in cells of patients under natalizumab treatment and up-regulated during relapse, supporting a regulatory role in MS immunopathogenesis. MiR-126 expression correlated with the expression of POU2AF1, a regulator of Spi-B that binds to the promoter/enhancer sequences of JC virus (JCV), the pathogen of progressive multifocal leukoencephalopathy (PML), a rare complication of natalizumab treatment. The same trend was found for Spi-B. Strong up-regulation of both genes appeared to be treatment duration-dependent. Specific inhibition experiments supported the link between the expression of miR-126 and POU2AF1/Spi-B. Our findings provided deeper insight into the mode of action of natalizumab, with possible implications for understanding both the effects of natalizumab on MS activity and its specific adverse event profile.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Clinical Neuroimmunology (Derfuss/Lindberg)
UniBasel Contributors:Derfuss, Tobias Johannes and Lindberg Gasser, Raija L.P.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:21 Jul 2020 14:40
Deposited On:21 Jul 2020 14:40

Repository Staff Only: item control page