Abstract

John Cunningham virus (JCV) causes rare, but potentially life-threatening progressive multifocal leukoencephalopathy (PML) in natalizumab-treated multiple sclerosis (MS) patients. Beside JCV index, there is currently no other factor for further risk stratification. Because smoking was reported as potential risk factor for several viral and bacterial infections, we aimed to investigate whether smoking could increase the risk for JCV infection in MS patients. We screened our database of the MS Clinic of the Department of Neurology, Medical University of Innsbruck, Austria, for patients with known smoking status and test result for anti-JCV antibody index as determined by two-step ELISA at Unilabs, Copenhagen, Denmark. In a representative cohort of 200 MS patients with a rate of 36% current smokers plus 6% former smokers, we were not able to detect any association between smoking and JCV status. Furthermore, there was no association between smoking status and anti-JCV antibody index. Smoking does not seem to be a risk factor for JCV infection in MS patients and, therefore, does not represent a suitable marker for PML-risk stratification under treatment with natalizumab.

Highlights

  • Progressive multifocal leukoencephalopathy (PML) is a rare, but potentially life-threatening adverse event during treatment with natalizumab (Tysabri®, Biogen Idec) in multiple sclerosis (MS) patients [1]

  • Since smoking is an assessable risk factor, we aimed to investigate a possible coincidence of smoking and John Cunningham virus (JCV) infection in MS patients in order to detect a potential influence of respiratory tract in transmission of JCV

  • (0.080–4.030) with no significant difference as compared to non-smokers (p value of 0.474). We included those patients in our analyses of whom smoking status before, during, and after onset of MS as well as at least one JCV test were available which resulted in a study cohort of n = 200

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Summary

Introduction

Progressive multifocal leukoencephalopathy (PML) is a rare, but potentially life-threatening adverse event during treatment with natalizumab (Tysabri®, Biogen Idec) in MS patients [1]. It is caused by reactivation of John Cunningham virus (JCV). Recent studies showed JCV prevalence rates around 55–60% in adult MS patients [2,3,4,5], of whom only a few eventually develop PML This underscores the urgent need to further stratify anti-JCV antibody positive patients, i.e., to detect possible risk factors for JCV infection and reactivation. The only confirmed marker which allows narrowing the high PML-risk group within JCV positive patients is JCV index [6]

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