Friday, 1 August 2014

JVC responses in young MSers

Any changes on the JC virus front for clinical practice? #MSBlog #MSResearch

"Two more papers on JC virus and MS; this is becoming a mini-field of expertise. As you already know if you are JCV negative, i.e. you have not been exposed to the virus and hence don't have the virus in your body the chance of you getting PML is very low. This does not mean it is zero as you can get exposed to virus as part of everyday life. In adults the seroconversion rate is quoted as being somewhere between 0.5% and 2% per year. The first study below looks at pediatric MSers and quotes a seroconversion rate of over 4% per year. Why? Maybe children and adolescents with MS are at higher risk of getting infected with the JC virus due to higher level of exposure? We think JCV is transmitted in urine and saliva. Maybe children/adolescents wash their hands less frequently and get exposed to saliva from different people, i.e. kiss more people, than adults? These results don't change clinical practice in that if  you are JCV negative and are on natalizumab you need you JCV status checked every 6 months and if you seroconvert you need to discuss strategies to de-risk the treatment by switching to an alternative agent."

"The second paper below suggests that a small number of JCV seronegative MSers may still be infected with the virus as they were show to have the virus in the urine. I don't buy this finding as the assay the investigator's used  to detect the virus is ultra-sensitive and is notorious for producing false-positive results; 2 patients had only 1 positive test and 1 patient 2 positive urine tests. In other words these results may be false-positive due to laboratory error. What is needed is these MSers is for these viral isolates to be ssequenced to see if they are the same, i.e. due to laboratory error. The latter has been shown in a previous study and confirmed at least in my mind that the urine PCR result was  a false positive finding. There is a possibility, however, that the virus may appear in the urine first before antibodies appear; this did not appear to be the case in these 3 MSers as all of them remained seronegative despite being retested 12, or more, months later. Does this paper change clinical practice? No it doesn't. I would not rely on urine screening to assess whether or not you are JCV positive; the assay may be too sensitive and liable to laboratory error."

Epub 1: Huppke et al. JC virus antibody status in a paediatric multiple sclerosis cohort: Prevalence, conversion rate and influence on disease severity. Mult Scler. 2014 Jul.

BACKGROUND: Because of the emergence of novel therapies for MS and the associated increased risk of progressive multifocal leukoencephalopathy (PML), John Cunningham (JC) virus infection has become a focus of interest for neurologists. However, little is known about JC virus infection in paediatric MS to date.

OBJECTIVE: We aimed to analyze the prevalence of anti-JC virus antibodies, the conversion rate and the influence of the anti-JC virus antibody status on the clinical course in a large pediatric MS cohort.

METHODS: Anti-JC virus antibodies were analyzed in serum samples within six months of disease onset and during the course of the disease. Clinical data were extracted from a pediatric MS databank.

RESULTS: A total of 51.6% of 256 MSers were found to be positive for anti-JC virus antibodies at onset of disease. No correlation between antibody status and clinical course was seen. Analyzing 693 follow-up serum samples revealed high titer stability, and an annual conversion rate of 4.37% was seen.

CONCLUSION: No evidence was found that seropositivity for anti-JC virus antibodies influences the clinical course. Surprisingly, seroprevalence for anti-JC virus antibodies was more than twice as high as anticipated in this age group, raising the question of whether the infection increases the risk of MS development.

Epub 2: Delbue et al. JC virus urinary excretion and seroprevalence in natalizumab-treated multiple sclerosis patients. J Neurovirol. 2014 Jul 23.

Background: The risk of developing PML, as a consequence of infection/reactivation with JC virus (JCV), is consistent in natalizumab-treated MSers, with 430 cases of PML reported so far. The risk of PML is higher in JCV seropositive MSers, and it is recommended that only MSers without JCV antibodies should be enrolled in the treatment postulating that they do not have JCV infection.

Methods: We have studied 42 natalizumab-treated MSers, and urine and blood were collected monthly for up to 60 months. JCV and BK virus (BKV) DNA presence was verified using quantitative real-time PCR assays, and serum anti-JCV antibodies were measured with the Stratify and/or Stratify DxSelect tests. 

Results: JCV and BKV DNA were not found in the blood samples, whereas they were found at least once in the urine of 21 of 42 (50 %) and of 25/42 (59.5 %) MSers, respectively. JCV DNA urinary shedding increased up to month 24 of natalizumab treatment (45.2 %), and the effect of time was significant for JCV (p = 0.04), but not for BKV (p = 0.39). JCV viruria and seropositivity did not completely correlate, since three MSers shedding JCV DNA in the urine were seronegative according to the serological tests.

Conclusion: The results indicated that natalizumab therapy may increase the rate of JCV urinary shedding. Additionally, we confirmed that the identification of JCV carriers cannot solely rely on serological tests, but sensitive methods for viral DNA detection should be adopted to more precisely identify the truly JCV uninfected cases.

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