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The CSF JCV antibody index for diagnosis of natalizumab-associated PML

Ann Neurol. 2014 Apr 11. doi: 10.1002/ana.24153. [Epub ahead of print]

Authors/Editors: Warnke C, von Geldern G, Markwerth P, Dehmel T, Hoepner R, Gold R, Pawlita M, Kümpfel T, Mäurer M, Stangel M, Wegner F, Hohlfeld R, Straeten V, Limmroth V, Weber T, Hermsen D, Kleinschnitz C, Hartung HP, Wattjes MP, Svenningson A, Major E, Olsson T, Kieseier BC, Adams O.
Publication Date: 2014

Abstract

Background: 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. Objective: To assess the complementary value of a CSF JCV antibody index (AIJCV ) in the diagnosis of natalizumab-associated PML. Methods: In 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML AIJCV was assessed. Sera and CSF were tested in a capture ELISA, using JCV-VP1 fused to glutathione S-transferase (GST) as antigen. Albumin levels and total IgG concentration were determined by immunonephelometry, and the AIJCV was calculated as published. Results: Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AIJCV >1.5, while this was seen in none of the controls (p<0.0001). At time of the first positive qPCR for JCV-DNA, 11/20 (55%) of patients with natalizumab-associated PML had an AIJCV >1.5. JCV-DNA levels of <100 copies/ml were seen in 14/20 (70%) of these patients of which 8 (57%) demonstrated an AIJCV >1.5. Interpretation: Determination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML..

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