期刊
ANNALS OF NEUROLOGY
卷 76, 期 6, 页码 792-801出版社
WILEY-BLACKWELL
DOI: 10.1002/ana.24153
关键词
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资金
- Research Commission of Heinrich Heine University, Dusseldorf [HHU]
- German Ministry for Education and Research (BMBF
- German Competence Network MS [KKNMS], Natalizumab Pharmacovigilance Study) [01GI1002]
- European Committee for Treatment and Research
- European Union [115303]
- European Federation of Pharmaceutical Industries and Associations companies
- Walter and Ilse Rose Foundation
- German Research Foundation [DFG CRC TRR128]
- BMBF (KKNMS)
- Niedersachsen Research Network on Neuroinfectiology of the Ministry of Science and Culture of Lower Saxony
ObjectiveProgressive 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. MethodsAI(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. ResultsTwenty-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. InterpretationDetermination 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
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