Anti-JC virus (JCV) antibody prevalence in the JCV Epidemiology in MS (JEMS) trial.

BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) is caused by reactivation of JC virus (JCV) infection due to combined host and viral factors. Anti-JCV antibodies provide a means to assess JCV exposure and stratify PML risk. The reported seroprevalence of anti-JCV antibodies varies from 39% to 91% depending on assay methodology and population studied. A two-step anti-JCV antibody assay (STRATIFY JCV™; Focus Diagnostics, Cypress, CA, USA) detected anti-JCV antibodies in approximately 55% of multiple sclerosis (MS) patients. This study describes the prevalence of anti-JCV antibodies in a large, multinational MS population. METHODS: This cross-sectional epidemiology study was designed to enroll a minimum of 2000 patients with an MS diagnosis of any type, irrespective of treatment, from Europe, Canada and Australia. Anti-JCV antibody prevalence was determined by STRATIFY JCV; the effects of demographic and disease characteristics were evaluated. RESULTS: A total of 7724 patients from 10 countries participated in the study. Overall anti-JCV antibody prevalence was 57.1% (95% confidence interval 56.0%-58.2%). Seroprevalence was significantly associated with increasing age, gender and country of current residence (P < 0.0001). No significant differences in anti-JCV antibody prevalence were associated with MS disease characteristics, including duration and type of MS and number and duration of MS therapies. CONCLUSIONS: Overall seroprevalence of anti-JCV antibodies in MS patients from Europe, Canada and Australia was consistent with previous studies using the STRATIFY JCV assay. Anti-JCV prevalence differed significantly by age, gender and country, but no geographical pattern was evident. Disease and treatment type were not associated with differences in anti-JCV antibody status.

Longitudinal analyses of anti-JCV antibody index for risk assessment of progressive multifocal leukoencephalopathy.

Risk assessment for natalizumab-associated progressive multifocal leukoencephalopathy (Nat-PML) comprises the anti-JC virus (JCV) antibody index (AI). The anti-JCV AI was longitudinally determined in a natalizumab-treated MS cohort (Nat-MS, n = 468) and samples of Nat-PML patients (n = 15). In Nat-MS, the median AI was 0.8 (25th to 75th percentile, 0.2-2.8) with an intra-individual coefficient of variation (CV) of 9.8% (4.8-17.6). Patients with an AI ≤ 0.9 exhibited higher CV. The AI was higher (3.4 (3.1-3.6)) in samples before Nat-PML diagnosis than in seropositive Nat-MS (2.4 (1.0-3.4), n = 298, p = 0.010). AIs ≥ 3.0 were associated with a 14.5-fold (95% CI 2.3-90.4) increased PML risk (p = 0.002). Groups with an AI below 1.5 exhibit higher variability or even serostatus fluctuation. AI dynamics require further investigation.