Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients.
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.
Biodonostia Health Research Institute, San Sebastián, SpainSpanish network on Multiple Sclerosis.
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M
Muñoz-Culla
Biodonostia Health Research Institute, San Sebastián, SpainSpanish network on Multiple Sclerosis.
H
H
Irizar
Spanish network on Multiple SclerosisBiodonostia Health Research Institute, San Sebastián, Spain/Hospital Universitario Donostia, San Sebastián, Spain.
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T
Castillo-Triviño
Biodonostia Health Research Institute, San Sebastián, SpainSpanish network on Multiple Sclerosis.
M
M
Sáenz-Cuesta
Biodonostia Health Research Institute, San Sebastián, SpainSpanish network on Multiple Sclerosis.
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L
Sepúlveda
Biodonostia Health Research Institute, San Sebastián, Spain.
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I
Lopetegi
Biodonostia Health Research Institute, San Sebastián, Spain/Hospital Universitario Donostia, San Sebastián, Spain/University of the Basque Country (UPV-EHU), San Sebastián, Spain/Centro de Investigación Biomédica en red Enfermedades Neurodegenerativas (CIBERNED).
A
A
López de Munain
Spanish network on Multiple SclerosisBiodonostia Health Research Institute, San Sebastián, Spain/Hospital Universitario Donostia, San Sebastián, Spain.
J
J
Olascoaga
University of California at San Francisco, USA.
S E
SE
Baranzini
Biodonostia Health Research Institute, San Sebastián, SpainSpanish network on Multiple Sclerosis david.otaegui@biodonostia.org.
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D
Otaegui
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab
D061067:Antibodies, Monoclonal, Humanized; C531888:MIRN125 microRNA, human; C572916:MIRN320 microRNA, human; C569688:MIRN629 microRNA, human; C571933:MIRN642 microRNA, human; D035683:MicroRNAs; D000069442:Natalizumab; C487931:mirnlet7 microRNA, human
Adverse effects; biomarker; miRNA expression; microRNA; multiple sclerosis; natalizumab; progressive multifocal leukoencephaly; risk factors