Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis

• Published in: Multiple sclerosis Vol. 21; no. 14; pp. 1823 - 1832
• Main Authors: Kohlmann, Rebekka, Salmen, Anke, Chan, Andrew, Knabbe, Cornelius, Diekmann, Jürgen, Brockmeyer, Norbert, Skaletz-Rorowski, Adriane, Michalik, Claudia, Gold, Ralf, Überla, Klaus
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2015; Sage Publications Ltd
• Subjects: Adolescent; Adult; Aged; Antibodies, Viral - blood; Child; Disease Susceptibility; Female; Herpes Zoster - blood; Herpesvirus 3, Human - immunology; HIV Infections - blood; Humans; Immunoglobulin G; Immunologic Factors - adverse effects; Male; Middle Aged; Multiple Sclerosis - blood; Multiple Sclerosis - drug therapy; Natalizumab - adverse effects; Virus Activation - drug effects; Young Adult; blood donors; neurotropic virus; risk factors; herpes zoster; virus reactivation; multiple sclerosis; immunosuppression; autoimmune disease; subclinical reactivation; varicella-zoster virus; Adverse events; JC virus; human immunodeficiency virus; antibodies; natalizumab
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458515576984

Background: Serious adverse drug reactions of disease-modifying drugs in multiple sclerosis (MS) therapy may include enhanced susceptibility to reactivation of neurotropic herpes viruses like varicella-zoster virus (VZV) and the John Cunningham (JC) polyomavirus. Objective: Because symptomatic reactivation of these viruses are rare events, we determined the incidence of rises in anti-VZV IgG antibody levels as a potential marker for enhanced susceptibility to subclinical and symptomatic reactivation of neurotropic viruses. Methods: Anti-VZV IgG levels were measured in paired serum samples taken 6–8 months apart from natalizumab-treated MS patients, healthy blood donors and human immunodeficiency virus (HIV) infected patients. Results: The incidence of significant rises in anti-VZV IgG levels in natalizumab-treated MS patients was 4.26 per 100 person-years, which was significantly higher than in healthy blood donors. Retrospective evaluation of the available medical records of patients with rises of anti-VZV IgG levels did not reveal herpes zoster (i.e. shingles) manifestations. Conclusions: The increased incidence of significant rises of anti-VZV IgG levels in natalizumab-treated MS patients might indicate an association of natalizumab treatment of MS with an elevated risk of a subclinical VZV reactivation and/or reinfection events. Whether this is predictive of an increased risk of herpes zoster or even symptomatic reactivation of other neurotropic viruses remains to be determined in larger prospective studies.