Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort.
Trampe, A.K. MSc; Hemmelmann, C. PhD; Stroet, A. MD; Haghikia, A. MD; Hellwig, K. MD; Wiendl, H. MD; Goelz, S. PhD; Ziegler, A. MD; Gold, R. MD; Chan, A. MD
78(22):1736-1742, May 29, 2012.
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Objective: To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assess anti-JCV serostatus in samples obtained before diagnosis of progressive multifocal leukoencephalopathy (PML).
Methods: This was a blinded, retrospective cross-sectional and longitudinal analysis for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples obtained from 2,253 patients nationwide for routine testing for anti-natalizumab antibodies during open-label treatment between 2007 and 2010.
Results: Of the natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV antibodies. The rate of seropositivity was higher in males and increased with age, with a plateau between age intervals 20-29 and 30-39 years. In longitudinal analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to seropositive status over 7.7 months; 4.7% reverted from antibody-positive to seronegative status over 7.9 months. Antibody levels, especially in the latter group, were low, indicating fluctuations around the lower cut point of the assay. Neither anti-JCV serostatus nor antibody levels were associated with immunosuppressive pretreatment, duration of natalizumab treatment, or anti-natalizumab antibodies. All samples obtained from 10 patients who developed PML were seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2 samples at diagnosis). Antibody levels in these samples were higher than those in samples from seropositive patients who did not develop PML.
Conclusions: These data argue for the potential clinical utility of JCV serology for PML risk stratification. However, further investigations of fluctuations in serostatus and of antibody levels for a more precise understanding of the predictive value are warranted.
GLOSSARY: CI: confidence interval
IgG: immunoglobulin G
JCV: JC virus
MS: multiple sclerosis
nOD450: normalized optical density
PML: progressive multifocal leukoencephalopathy
RR: relative risk
(C) 2012 American Academy of Neurology