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.