Research: new assay for JC Virus

#MSBlog: Has your JC virus serological test flipped from being negative to positive? It may be due to the increased sensitivity of the new StratifyJCV assay.

Epub: Warnke et al. An assay to quantify species-specific anti-JC virus antibody levels in MS patients. Mult Scler. 2013 Feb.

BACKGROUND: The StratifyJCV® test is a qualitative assay to classify MSers as anti-JC virus (JCV) antibody positive or negative. Quantification of anti-JCV antibody levels in serum and cerebrospinal fluid (CSF) of MSers might add to the progressive multifocal leukoencephalopathy (PML) risk assessment.

OBJECTIVE: The objective of this study is to test sera of MSers in a quantitative anti-JCV antibody assay, and to compare the results with pre-existing data from the StratifyJCV® test.

METHODS: Sera of a total of 175 MS MSers and matched non-MS-controls were tested for anti-JCV antibodies using glutathione S-transferase-tagged-VP1 (VP1 is a bit of the virus and the glutathione S transferase is marker protein created by molecular engineering to help produce and purify the viral VP1 protein) as antigen. Antibody reactivity was quantified in arbitrary units using human immunoglobulin as standard.

RESULTS: The comparison of our assay with StratifyJCV® showed good inter-assay agreement (kappa 0.6), and strong correlation for antibody reactivity (r(2) = 0.94). Discordant samples had low-reactive positivity, and a higher proportion (13% vs. 4%) tested positive in the StratifyJCV® test only.

CONCLUSIONS: The method presented is a tool for the reliable quantification of anti-JCV antibodies, which demonstrates good agreement with results from StratifyJCV®. In contrast to StratifyJCV®, they pre-adsorbed all of the sera with BK virus (BKV) VP1 protein to reduce cross-reactivity. This step may account for a higher species-specificity in their assay. As such, their assay might be a promising additional tool for PML risk assessment.

"The new StratifyJCV assay from Biogen-Idec is more sensitive and specific than the version one of the assay and other JCV assays out there. This has resulted in quite a large number of MSers flipping from being negative to positive. These MSers tend to have low levels of antibodies suggesting they are borderline positive. In comparison MSers who become positive from being infected with JC virus from exposure to the virus tend to have high titres. This is all academic at present as we treat both these groups of MSers as being infected with the virus and therefore being at high-risk of developing PML as a complication of natalizumab treatment. However, there is some emerging data and theoretical reasons why these groups of JCV seropositive MSers may be different; the MSers who seroconvert with low titres at the lower end of the positive range may be false positives, whereas those with high titres are true seroconverters due to recent exposure to the virus. Hopefully, Biogen-Idec will be able to answer this question when they have enough data in the future. Why is this important? It may be important if you happen to one of these seroconverters and don't want to switch your treatments."

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