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

作者：Munoz Culla M; Irizar H; Castillo Trivino T; Saenz Cuesta M; Sepulveda L; Lopetegi I; Lopez de Munain A; Olascoaga J; Baranzini S E; Otaegui D^*

来源：Multiple Sclerosis, 2014, 20(14): 1851-1859.

DOI：10.1177/1352458514534513

• Adverse effects
• biomarker
• microRNA
• miRNA expression
• multiple sclerosis
• natalizumab
• progressive multifocal leukoencephaly
• risk factors

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2014-12