Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients

Mult Scler. 2014 Dec;20(14):1851-9. doi: 10.1177/1352458514534513. Epub 2014 May 22.

Abstract

Background: Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability; however, it has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). The differential expression of microRNA (miRNA), the small non-coding RNAs that regulate gene expression, in natalizumab-treated patients has been reported and miRNA have also been described as good candidates for disease biomarkers.

Objective: To characterize the effect of natalizumab therapy on the miRNA expression pattern and to search for miRNAs that can predict PML on an individual basis.

Methods: The expression of 754 microRNAs was measured in blood samples from 19 relapsing-remitting MS patients at three time points during natalizumab therapy, using TaqMan OpenArray panels. Two patients included in this study developed PML after more than 2 years of therapy.

Results: We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy (t6). Furthermore, we observed a differential expression of another three miRNAs (miR-320, miR-320b and miR-629) between the PML and non-PML groups after 12 months of treatment (t12); and a positive correlation was found between therapy time and the expression of miR-320.

Conclusions: Natalizumab modified the expression levels of three miRNAs after a 6-month treatment. We suggest miR-320, miR-320b and miR-629 as possible biomarkers for individual PML risk assessment.

Keywords: Adverse effects; biomarker; miRNA expression; microRNA; multiple sclerosis; natalizumab; progressive multifocal leukoencephaly; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Case-Control Studies
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Humans
  • Leukoencephalopathy, Progressive Multifocal / blood
  • Leukoencephalopathy, Progressive Multifocal / chemically induced
  • Leukoencephalopathy, Progressive Multifocal / genetics*
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Natalizumab

Substances

  • Antibodies, Monoclonal, Humanized
  • MIRN125 microRNA, human
  • MIRN320 microRNA, human
  • MIRN629 microRNA, human
  • MIRN642 microRNA, human
  • MicroRNAs
  • Natalizumab
  • mirnlet7 microRNA, human