Anti-JC virus levels and PML risk

Plavina T, Subramanyam M, Bloomgren G, Richman S, Pace A, Lee S, Schlain B, Campagnolo D, Belachew S, Ticho B. Anti-JCV antibody levels in serum or plasma further define risk of natalizumab-associated PML. Ann Neurol. 2014 Oct 1. doi: 10.1002/ana.24286. [Epub ahead of print]

Objective: The increased risk of progressive multifocal leukoencephalopathy (PML) with natalizumab treatment is associated with the presence of anti-JC virus (JCV) antibodies. We analyzed whether anti-JCV antibody levels, measured as index, may further define PML risk in seropositive patients. 

Methods: The association between serum or plasma anti-JCV antibody levels and PML risk was examined in anti-JCV antibody positive multiple sclerosis (MS) patients from natalizumab clinical studies and post-marketing sources. For PML and non-PML patients, the probabilities of having an index below and above a range of anti-JCV antibody index thresholds were calculated using all available data and applied to the PML risk stratification algorithm. Longitudinal stability of anti-JCV antibody index was also evaluated. 
Results: Anti-JCV antibody index data were available for serum/plasma samples collected more than 6 months prior to PML diagnosis from 71 natalizumab-treated PML patients and 2,522 non-PML anti-JCV antibody positive patients. In patients with no prior immunosuppressant use, anti-JCV antibody index distribution was significantly higher in PML patients than in non-PML patients (p < 0.0001). Among patients who were anti-JCV antibody negative at baseline in the AFFIRM and STRATIFY-1 trials, 97% remained consistently negative or below an index threshold of 1.5 over 18 months. Retrospective analyses of pre-PML samples collected longitudinally from PML patients displayed sustained higher anti-JCV antibody index over time. 
Interpretation: Anti-JCV antibody levels in serum/plasma, measured as index, may differentiate PML risk in anti-JCV antibody positive MS patients with no prior immunosuppressant use. Continued evaluation of anti-JCV antibody index and PML risk is warranted.

Serum is the fluid that is found in blood after the blood has clotted. Plasma is the cell free fluid in blood which has been stopped from clotting. In this study they looked at the blood from MSers who unfortunately developed PML after taking tysabri. Their anti-JC virus antibody response was elevated compared to people who did not have  antibodies to JC virus.

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