Research: JC Virus in Urine

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Laroni A et al. Urinary JCV-DNA Testing during Natalizumab Treatment May Increase Accuracy of PML Risk Stratification.J Neuroimmune Pharmacol. 2012 May 16. [Epub ahead of print]
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. 

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MouseDoctor

5 comments

  • Re: "Is JCV dna in urine a more reliable test than antiJV antibodies in blood?"

    No. If you have the virus you tend to shed intermittently into the urine. Whereas once your immune system has seen the virus and produced antibodies they tend to remain positive for decades and possibly for life. We call this immunological memory. Therefore serology is the better test.

  • Prof G, how does this answer equate with the question and answer in the topic below as to people becoming seronegative?

  • Re: "Prof G, how does this answer equate with the question and answer in the topic below as to people becoming seronegative?"

    No assay is perfect and there is always a small number of false positives who if tested again come back as being negative. We think this occurs in 0.5-2.0% of people. Another cause for this is cross-reactivity to related viruses that share some of protein structure with JC virus. These false positive or cross-reactive tests are usually at a very low level, i.e. a low titre. It looks as if all the MSers who go onto develop PML have relatively high titres. Finally you can become seronegative with immunosuppression and with age (immunosenescence).

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