Cerebrospinal fluid JC virus antibody index for diagnosis of natalizumab‐associated progressive multifocal leukoencephalopathy. Issue 6 (8th May 2014)

• Record Type: Journal Article
• Authors: Warnke, Clemens; von Geldern, Gloria; Markwerth, Philipp; Dehmel, Thomas; Hoepner, Robert; Gold, Ralf; Pawlita, Michael; Kümpfel, Tania; Mäurer, Mathias; Stangel, Martin; Wegner, Florian; Hohlfeld, Reinhard; Straeten, Vera; Limmroth, Volker; Weber, Thomas; Hermsen, Derik; Kleinschnitz, Christoph; Hartung, Hans‐Peter; Wattjes, Mike P.; Svenningson, Anders; Major, Eugene; Olsson, Tomas; Kieseier, Bernd C.; Adams, Ortwin
• Is Part Of: Annals of neurology. Volume 76:Issue 6(2014:Dec.)
• Page Start: 792
• Page End: 801
• Publication Date: 2014-05-08
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24153
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ana24153-sec-0001" sec-type="section"> <title>Objective</title> <p>Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AI<sub>JCV</sub>) in the diagnosis of natalizumab‐associated PML.</p> </sec> <sec id="ana24153-sec-0002" sec-type="section"> <title>Methods</title> <p>AI<sub>JCV</sub> was assessed in 37 cases of natalizumab‐associated PML and 89 MS‐patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme‐linked immunosorbent assay, using JCV‐VP1 fused to glutathione S‐transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AI<sub>JCV</sub> was calculated as published.</p> </sec> <sec id="ana24153-sec-0003" sec-type="section"> <title>Results</title> <p>Twenty‐six of 37 (70%) patients with natalizumab‐associated PML exhibited an AI<sub>JCV</sub> > 1.5, whereas this was seen in none of the controls (<italic>p</italic> < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab‐associated PML had an AI<sub>JCV</sub> > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AI<sub>JCV</sub> > 1.5.</p> </sec> <sec id="ana24153-sec-0004" sec-type="section"> <title>Interpretation</title> <p>Determination of the AI<sub>JCV</sub> could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab‐associated PML. Ann Neurol 2014;76:792–801</p> </sec> </abstract>