Anti‐JC virus antibodies: Implications for PML Risk Stratification
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- 24 August 2010
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 68 (3), 295-303
- https://doi.org/10.1002/ana.22128
Abstract
Objective A study was undertaken to establish an enzyme-linked immunosorbent assay (ELISA) to detect JC virus (JCV)-specific antibodies in multiple sclerosis (MS) patients, and to evaluate its potential utility for identifying patients at higher or lower risk (ie, risk stratification) of developing progressive multifocal leukoencephalopathy (PML). Methods A 2-step assay for detecting and confirming the presence of anti-JCV antibodies in human serum and plasma was developed and demonstrated to be both sensitive and specific. ELISA cutpoints were statistically established using sera from >800 MS patients from natalizumab clinical studies. Subsequently, this assay was used to determine the presence of anti-JCV antibodies in natalizumab-treated PML patients where serum samples were collected 16-180 months prior to the diagnosis of PML. Results In our evaluation of natalizumab-treated MS patients, 53.6% tested positive for anti-JCV antibodies, with a 95% confidence interval of 49.9 to 57.3%. The false-negative rate of the ELISA was calculated to be approximately 2.5%, with an upper 1-sided confidence limit of 4.4%. Notably, we observed anti-JCV antibodies in all 17 available pre-PML sera samples, which was significantly different from the 53.6% seropositivity observed in the overall MS study population (p < 0.0001). Interpretation This 2-step assay provides a means to classify MS patients as having detectable or not detectable levels of anti-JCV antibodies. The finding that all 17 of the pre-PML samples that were available tested seropositive, and none tested seronegative, warrants further research on the clinical utility of the anti-JCV antibody assay as a potential tool for stratifying MS patients for higher or lower risk of developing PML. Ann Neurol 2010Keywords
This publication has 30 references indexed in Scilit:
- Prevalence and stability of antibodies to the BK and JC polyomaviruses: a long-term longitudinal study of AustraliansJournal of General Virology, 2010
- Progressive Multifocal Leukoencephalopathy in Patients on Immunomodulatory TherapiesAnnual Review of Medicine, 2010
- Adaptive Mutations in the JC Virus Protein Capsid Are Associated with Progressive Multifocal Leukoencephalopathy (PML)PLoS Genetics, 2009
- Progressive Multifocal Leukoencephalopathy and Use of Mycophenolate Mofetil After Kidney TransplantationTransplantation, 2008
- Infectious Complications Associated with Alemtuzumab Use for Lymphoproliferative DisordersClinical Infectious Diseases, 2006
- Rearrangement Patterns of JC Virus Noncoding Control Region from Different Biological SamplesJournal of NeuroVirology, 2003
- Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in HumansJNCI Journal of the National Cancer Institute, 2003
- Co-infection with two JC virus genotypes in brain, cerebrospinal fluid or urinary tract detected by direct cycle sequencing of PCR productsJournal of NeuroVirology, 1996
- Persistence of DNA Sequences of BK Virus and JC Virus in Normal Human Tissues and in Diseased TissuesThe Journal of Infectious Diseases, 1983
- The persistence of papovavirus BK DNA sequences in normal human renal tissueJournal of Medical Virology, 1981