Research: JC Virus seropositivity in MSers

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OBJECTIVE: To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis
(MS) cohort treated with natalizumab in the postmarketing setting and
to assess anti-JCV serostatus in samples obtained before diagnosis of
progressive multifocal leukoencephalopathy (PML).

METHODS: This
was a blinded, retrospective cross-sectional and longitudinal analysis
for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood
samples obtained from 2,253 patients nationwide for routine testing for
anti-natalizumab antibodies during open-label treatment between 2007
and 2010.

RESULTS: Of the natalizumab-treated patients
with MS, 58.8% tested positive for anti-JCV antibodies. The rate of
seropositivity was higher in males and increased with age, with a
plateau between age intervals 20-29 and 30-39 years. In longitudinal
analyses, 19 of 194 (9.8%) patients converted from anti-JCV
antibody-negative to seropositive status over 7.7 months; 4.7% reverted
from antibody-positive to seronegative status over 7.9 months. Antibody
levels, especially in the latter group, were low, indicating
fluctuations around the lower cut point of the assay. Neither anti-JCV
serostatus nor antibody levels were associated with immunosuppressive
pretreatment, duration of natalizumab treatment, or anti-natalizumab
antibodies. All samples obtained from 10 patients who developed PML were
seropositive (13 samples before PML diagnosis [2.0-37.6 months]; 2
samples at diagnosis). Antibody levels in these samples were higher than
those in samples from seropositive patients who did not develop PML.

CONCLUSIONS:These
data argue for the potential clinical utility of JCV serology for PML
risk stratification. However, further investigations of fluctuations in
serostatus and of antibody levels for a more precise understanding of
the predictive value are warranted.

 

JC virus is one of the major causes of PML, that can occur as a consequence of immunosuppression. It is a risk factor for Tysabri-associated PML that can shift the balance from 1 in 100 chance to one in 10,000 chance of developing PML. This study in Germany shows about 60% of Msers have the virus, which is essentially the same as the general population.  The study indicates that some people become seronegative which means that they stop having detectable JC virus-specific in their blood.

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MouseDoctor

4 comments

  • Many questions-

    Re 'These data argue for the potential clinical utility of JCV serology for PML risk stratification'
    Why are they saying this now? I thought the clinical utility was already established. This blog has many posts on PML risk stratification

    Re 'JC virus is one of the major causes of PML'
    Isn't JC virus the only cause? Are there other causes too?

    Re '4.7% reverted from antibody-positive to seronegative status'
    How can antibodies disappear and what does it mean for PML risk?

    Re 'Four subjects with JCV-DNA in urine and undetectable anti-JCV antibodies were retested for anti-JCV antibodies and three out of four resulted positive'
    How can this happen? If the urine has JCV DNA, shouldn't there be anti-JCV antibodies too?
    from the other post today

  • Re risk stratification..I agree with you mayeb they should read the blog.

    Antibodies have a natural half-time and dissappear from circulation unless new ones are made.

    In terms of PML risk it means some one perhaps tested negative may still harbor the virus.

    1 in 10,000 people that is seronegative can get PML based on the risks posed.

    The kidneys filter out alot of things and proteins are often broken down by the body before excretion. DNA can be detected by amplicification means and so low amounts of visus could be detected.

  • "If you have virus shouldn't you be antibody positive".

    Sometimes it takes time to sero convert. For example with HIV it can take weeks for you to become positive. So there can be a time lag before antibodies appear.

    Looking for DNA means you amplify the viral copy number up. So it may exists at vey low levels and may perhaps be sub-immunogenic.
    so it does not induce an antibody response.

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