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JCPyV microRNA in plasma inversely correlates with JCPyV seropositivity among long-term natalizumab-treated relapsing-remitting multiple sclerosis patients

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Abstract

Sensitive biomarkers are needed to better manage multiple sclerosis (MS) patients for natalizumab (NTZ)-associated risk of progressive multifocal leukoencephalopathy (PML). A currently used risk stratification algorithm, mainly based on JC polyomavirus (JCPyV) serology, has not led to a reduction of PML incidence. Therefore, this study was designed to evaluate the presence and prevalence of JCPyV miRNAs in plasma of NTZ-treated MS patients, and to explore their biomarker potential for NTZ-associated PML risk assessment. Altogether, 102 plasma samples from 49 NTZ-treated and 28 interferon-beta (IFN-β)-treated relapsing-remitting MS patients, and 25 healthy controls (HCs) were analyzed for jcv-miR-J1-5p (5p miRNA) and jcv-miR-J1-3p (3p miRNA) expression. The overall detection rate of 5p miRNA was 84% (41/49) among NTZ-treated patients, 75% (21/28) among IFN-β-treated patients, and 92% (23/25) in HCs. Relative 5p miRNA expression levels were lower in NTZ-treated patients as compared to patients treated with IFN-β (p = 0.027) but not to HCs. Moreover, 5p miRNA expression inversely correlated with anti-JCPyV antibody index among JCPyV seropositive long-term NTZ-treated patients (r = −0.756; p = 0.002). The overall detection rate of 3p miRNA was low. Our results suggest that JCPyV miRNA in plasma may be linked to the reactivation of persistent JCPyV, to enhanced virus replication, and eventually to the risk of developing PML among NTZ-treated MS patients. However, further study is warranted in a larger data set including samples from PML patients to confirm the clinical relevance of JCPyV miRNA as a sign of/in viral reactivation, and to identify its potential to predict developing PML risk.

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Acknowledgements

The authors thank Keijo Koivisto (Seinäjoki Central Hospital, Department of Neurology, Seinäjoki, Finland), Auli Verkkoniemi-Ahola (Department of Clinical Neurosciences, Helsinki University Central Hospital, Helsinki, Finland), and Laura Airas (Department of Clinical Neurosciences, Turku University hospital, Turku, Finland) for providing samples and clinical information on patients from their centers. The authors also thank Mika Helminen (School of Health Sciences, University of Tampere) for his advice in statistical analyses. The study was financially supported by the Tampere University Hospital Medical Fund, Pirkanmaa Regional Fund of the Finnish Cultural Foundation, Finnish MS Foundation, and Alfred Kordelin Foundation of Finland.

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Authors and Affiliations

  1. Neuroimmunology Unit, School of Medicine, University of Tampere, Tampere, Finland

    Pabitra Basnyat, Irina Elovaara & Sanna Hagman

  2. Department of Virology, Medicum, University of Helsinki and Helsinki University Hospital Laboratory, Helsinki, Finland

    Elina Virtanen & Eeva Auvinen

  3. Department of Neurology, Tampere University Hospital, Tampere, Finland

    Irina Elovaara

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  1. Pabitra Basnyat
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  2. Elina Virtanen
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Correspondence to Pabitra Basnyat.

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Basnyat, P., Virtanen, E., Elovaara, I. et al. JCPyV microRNA in plasma inversely correlates with JCPyV seropositivity among long-term natalizumab-treated relapsing-remitting multiple sclerosis patients. J. Neurovirol. 23, 734–741 (2017). https://doi.org/10.1007/s13365-017-0560-x

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