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Application of the CSF JCV antibody index to early natalizumab-associated progressive multifocal leukoencephalopathy
  1. Clemens Warnke1,2,
  2. Martijn T Wijburg3,4,
  3. Hans-Peter Hartung1,
  4. Joep Killestein4,
  5. Ortwin Adams5,
  6. Mike P Wattjes3
  1. 1 Department of Neurology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
  2. 2 Department of Neurology, University Hospital Cologne, Cologne, Germany
  3. 3 Department of Radiology & Nuclear Medicine, Neuroscience Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
  4. 4 Department of Neurology, Neuroscience Amsterdam, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
  5. 5 Institute for Virology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany
  1. Correspondence to Dr Clemens Warnke, Department of Neurology, University Hospital Cologne, Kerpener Strasse 62, Cologne 50937, Germany; clemens.warnke{at}uk-koeln.de

https://doi.org/10.1136/jnnp-2016-315298

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    Introduction

    Progressive multifocal leukoencephalopathy (PML) is a severe adverse event in patients with multiple sclerosis (MS) treated with natalizumab. Brain MRI can detect small PML lesions at an early disease stage.1 Therefore, MRI screening is recommended for patients at high risk of developing PML.2 Diagnosis of PML is confirmed by brain biopsy or detection of JC virus (JCV) DNA from cerebrospinal fluid (CSF).3 However, in spite of using ultrasensitive quantitative PCR (qPCR) protocols, patients with PML can be JCV DNA negative in CSF, hampering the diagnosis. Recently, we demonstrated that the detection of intrathecally produced anti-JCV IgG antibodies is highly specific for diagnosis of PML, making the so-called CSF JCV antibody index (AIJCV) a candidate tool for earlier diagnosing of PML in a proportion of natalizumab-associated PML patients.4

    The aim of this study was to assess the value of the AIJCV in a case series of natalizumab-treated patients with MS undergoing enhanced MRI pharmacovigilance for PML.

    Patients and methods

    Natalizumab-treated MS patients screened for PML using MRI (T2, fluid attenuation inversion recovery (FLAIR), diffusion weighted imaging) at the VU University Medical Center Amsterdam, and referrals, were included in the study. Patients with MRI suspicion of PML and a serum/CSF pair for assessment of the AIJCV at time of first MRI suspicion of PML were eligible. JCV DNA by qPCR and the AIJCV in CSF were determined at the Institute of Virology, University of Düsseldorf, Germany, and methods and cut-points (1.5 for the AIJCV) were applied as recently described.4 The study was approved by the local institutional review board, and written informed consent was obtained from all participants.

    Results

    Basic characteristics of the patients included are provided in the online supplementary table. Median age was 46 years, and five of eight patients (63%) were female. Six …

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    Footnotes

    • Contributors Study concept and design: CW, OA and MPW. Acquisition and analysis of data: all. Drafting of manuscript: CW, MTW. Critical revision of the manuscript for important intellectual content: all.

    • Competing interests CW: consulting and/or research funding: Bayer, Biogen, Novartis, TEVA. HPH: received honoraria for consulting and speaking at symposia from Bayer, Biogen, Genzyme, Merck Serono, Novartis Pharma, Roche and Teva Sanofi-Aventis. JK: accepted speaker and consulting fees from Merck Serono, Biogen, TEVA, Genzyme, Roche and Novartis. OA: accepted speakers honoraria and research funding from Biogen. MPW: accepted speaker and consulting fees from Biogen, Novartis, Roche and Genzyme.

    • Patient consent All patients signed a written informed consent stating that data and imaging can be used for research and education, approved by the local institutional review board at VUmc.

    • Provenance and peer review Not commissioned; externally peer reviewed.