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.
Labels: JC virus