Monitoring anti-JC virus antibody status in Natalizumabers

The second generation anti-JC virus antibody test has caused some anxiety. But it is not all bad news. #MSBlog #MSResearch 

“The launch of the Biogen-Idec 2nd generation anti-JCV serology assay has caused problems with a high number of MSers seroconverting to JCV positive and hence being at high risk of PML as a complication of natalizumab. The french study below indicates that 14.5% seroconverted with the new assay when less than 3% was expected to do so. Why?”

“The second generation 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. Those MSers who have low levels of antibodies are safe and indicates that they are borderline positive. In comparison MSers who become positive from being infected with JC virus from true exposure to the virus tend to have high titres. There is new data showing that 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.”

“The figures are from a poster that was presented at the European Neurological Society meeting earlier this year. The figures in the bottom table are derived from Table 2 above and present the data in a different way; i.e. as an absolute risk. These figures are derived from relatively small numbers, i.e. 51 cases of PML. As more cases emerge the data set will be updated. The implications of this data is that many MSers who are doing well on natalizumab and have low titres, or a low index, may choose to stay on natalizumab rather than switch. If you are on natalizumab and are JCV seropositive what level of risk are you prepared to take? I assume your judgement of your level of risk will be based on personal factors, e.g. how bad your MS was before you started natalizumab, and how you view your long term prognosis of MS.”

Epub: Outteryck et al. JC-virus seroconversion in multiple sclerosis patients receiving natalizumab. Mult Scler. 2013 Sep.

AIM: The objectives of this study were to evaluate the rate of JC virus (JCV) seroconversion/seroreversion in a French cohort of MSers receiving natalizumab (NTZ), describe the characteristics of this population, identify risk factors for JCV seropositivity and analyse the additional value of quantitative JCV serology results in this context.

METHODS: MSers from two French MS centres, whose JCV serological status in 2011 while receiving NTZ was known (n=357; first-generation enzyme-linked immunosorbent assay (ELISA) test (Gen1)), were proposed for inclusion in this study. They evaluated the rate of JCV seroconversion over a period of one year with a second-generation ELISA test (Gen2; n=303) and analysed the quantitative results.

RESULTS: Among the MSers with Gen2 JCV serology (n=303) that had been JCV-seronegative one year before (n=165), the rate of JCV seroconversion was 26.7% (44/165). We observed a higher proportion of anti-JCV antibody seroconverters (14.5%) than expected (≤3%) but also increasing index values of anti-JCV antibody over time.

CONCLUSION: Our data suggest that JCV reactivation occurs during NTZ therapy and leads to an increase in the anti-JCV antibodies titre, thus making them more easily detectable by the second-generation ELISA test.


6 thoughts on “Monitoring anti-JC virus antibody status in Natalizumabers”

  1. I've just been told I'm jcv+ and would also be very interested to know when this 2nd gen test started to be used. My previous negative result was from April 13.I have an appointment to discuss the results with my neuro next week. Should I expect to receive my JCV ab index?Thanks

    1. The 2nd generation assay or the 'Stratify JCV DX Select' was launched in March 2011. In this setting it is important to find out if the conversion is a low level/titre conversion or a high level/titre conversion. If the anti-JCV titre is high it is likely a true seroconversion. If the titre is a low positive it could be a false positive and I would then wait 6 months to see what happens to the titre. I have addressed this issue in the past.

    2. Thanks Prof G, really appreciate the quick response. Hopefully I'll find out my titre level at my appointment this week and then make a call.

  2. I tested – which is great but for the fires time I was given an index value of .18. What does that mean with a negative result?

  3. My index is I cannot remember if my doc said I was 2.1 or .21 big difference I realized. He did say that I am negative but I am having mri of spine and brain… and I am having symptoms which could be my ms but also listed for pml. Little anxious.

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