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Cerebrospinal fluid JC virus antibody index for diagnosis of natalizumab‐associated progressive multifocal leukoencephalopathy
Author(s) -
Warnke Clemens,
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 HansPeter,
Wattjes Mike P.,
Svenningson Anders,
Major Eugene,
Olsson Tomas,
Kieseier Bernd C.,
Adams Ortwin
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24153
Subject(s) - natalizumab , progressive multifocal leukoencephalopathy , jc virus , multiple sclerosis , cerebrospinal fluid , medicine , slow virus , antibody , virology , immunology , pathology
Objective 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 JCV ) in the diagnosis of natalizumab‐associated PML. Methods AI JCV 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 JCV was calculated as published. Results Twenty‐six of 37 (70%) patients with natalizumab‐associated PML exhibited an AI JCV > 1.5, whereas this was seen in none of the controls ( p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab‐associated PML had an AI JCV > 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 JCV > 1.5. Interpretation Determination of the AI JCV 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