The risk of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab for multiple sclerosis (MS)
is a serious concern. The presence of anti-JC virus antibodies is a
risk factor for PML development, but 2.5 % of the patients result
falsely-negative, while the prognostic relevance of testing JCV-DNA in
biological fluids of treated patients is debated. Aim of this work was
to evaluate the utility of testing JCV-DNA, together with anti-JCV
antibodies, in biological samples of treated patients as a tool for PML
risk stratification. 126 subjects from 5 MS Centers in Italy were
included in the study. We performed a cross-sectional study in 63
patients testing JCV-DNA in blood, peripheral blood cells and urine.
We
longitudinally assessed the presence of JCV-DNA in a cohort of 33
subjects, one of which developed PML. We could test retrospectively
serum samples from another PML case occurred during natalizumab therapy.
Anti-JCV antibodies and urinary JCV-DNA were both tested in 73
patients. No changes in JCV-DNA status occurred during natalizumab
treatment. The subject who developed PML in the longitudinal cohort had
detectable JCV-DNA in urine at all time-points while serum or blood from
both PML patients were always negative before the onset of disease and,
in one case, after.
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. In conclusion, testing JCV-DNA in urine is complementary to
testing anti-JCV antibodies in identifying patients at risk of PML.
When I first met Prof G in lab, he
was testing urine for biomarker studies. This study shows that sometimes
when you can't find JC virus in the blood by analysis for antibodies
you can find it in the urine. The difference is that you are looking for
the virus in the urine, but the immune response to the virus in the
blood.
