M Kolasa1, S Hagman1, A Verkkoniemi-Ahola2, L Airas3, K Koivisto4, I Elovaara1. 1. Neuroimmunology Unit, Medical School, University of Tampere, Tampere, Finland. 2. Department of Clinical Neurosciences, Helsinki University Central Hospital, Helsinki, Finland. 3. Department of Clinical Neurosciences, Turku University Hospital, Turku, Finland. 4. Department of Neurology, Seinäjoki Central Hospital, Seinäjoki, Finland.
Abstract
BACKGROUND: The risk of progressive multifocal leukoencephalopathy (PML) caused by the JC virus (JCV) is increased in patients with multiple sclerosis receiving biological therapies. OBJECTIVES: To determine the seroprevalence of anti-JCV antibodies in Finnish patients with multiple sclerosis (MS) and clinically isolated syndrome and to assess the clinical risk factors for JCV seropositivity. METHODS: The JCV seroprevalence was analyzed in 503 patients using a second-generation two-step ELISA. Sixty-seven patients underwent longitudinal serological evaluation over 4.5 years. RESULTS: The overall seroprevalence of JCV was 57.4%. The seropositivity was higher in men than in women, tended to increase with age, and was not affected by different immunomodulatory therapies. However, in patients with ongoing natalizumab treatment (n = 72), the anti-JCV antibody screening index was lower than in patients without such therapy [median 0.3 (range 0.1-3.1) vs 0.6 (0.1-3.1), respectively, P = 0.01]. Over 4.5 years, 4/19 (21%) initially seronegative patients converted to seropositivity, whereas 4/48 (8.3%) initially seropositive patients reverted to seronegativity. Fluctuations in serostatus were observed in 3/67 patients. CONCLUSION: The study confirmed a high anti-JCV antibody prevalence in patients with MS and its association with age and male gender but not with disease-modifying therapies. Our data suggest that therapy with natalizumab may cause a decrease in anti-JCV antibody levels, suggesting an immunosuppressive effect of natalizumab without an impact on JCV seroprevalence. The results of studies performed until now confirm the predictive value of anti-JCV antibody measurement in the assessment of PML risk; however, changes in serostatus need to be considered.
BACKGROUND: The risk of progressive multifocal leukoencephalopathy (PML) caused by the JC virus (JCV) is increased in patients with multiple sclerosis receiving biological therapies. OBJECTIVES: To determine the seroprevalence of anti-JCV antibodies in Finnish patients with multiple sclerosis (MS) and clinically isolated syndrome and to assess the clinical risk factors for JCV seropositivity. METHODS: The JCV seroprevalence was analyzed in 503 patients using a second-generation two-step ELISA. Sixty-seven patients underwent longitudinal serological evaluation over 4.5 years. RESULTS: The overall seroprevalence of JCV was 57.4%. The seropositivity was higher in men than in women, tended to increase with age, and was not affected by different immunomodulatory therapies. However, in patients with ongoing natalizumab treatment (n = 72), the anti-JCV antibody screening index was lower than in patients without such therapy [median 0.3 (range 0.1-3.1) vs 0.6 (0.1-3.1), respectively, P = 0.01]. Over 4.5 years, 4/19 (21%) initially seronegative patients converted to seropositivity, whereas 4/48 (8.3%) initially seropositive patients reverted to seronegativity. Fluctuations in serostatus were observed in 3/67 patients. CONCLUSION: The study confirmed a high anti-JCV antibody prevalence in patients with MS and its association with age and male gender but not with disease-modifying therapies. Our data suggest that therapy with natalizumab may cause a decrease in anti-JCV antibody levels, suggesting an immunosuppressive effect of natalizumab without an impact on JCV seroprevalence. The results of studies performed until now confirm the predictive value of anti-JCV antibody measurement in the assessment of PML risk; however, changes in serostatus need to be considered.
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