Rebekka Kohlmann1, Anke Salmen2, Andrew Chan2, Cornelius Knabbe3, Jürgen Diekmann3, Norbert Brockmeyer4, Adriane Skaletz-Rorowski4, Claudia Michalik5, Ralf Gold2, Klaus Überla6. 1. Department of Molecular and Medical Virology, Ruhr-University Bochum, Germany. 2. Department of Neurology, Sankt Josef-Hospital, Ruhr-University Bochum, Germany. 3. Institute of Laboratory and Transfusion Medicine, Heart and Diabetes Centre North Rhine-Westphalia, Ruhr-University Bochum, Bad Oeynhausen, Germany. 4. German Competence Network for HIV/AIDS; Department of Dermatology, Venerology and Allergology; Sankt Josef-Hospital; Ruhr-University Bochum; Germany. 5. Clinical Trials Center (ZKS), Cologne, Germany. 6. Department of Molecular and Medical Virology, Ruhr-University Bochum, Germany/Universitätsklinikum Erlangen, Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany klaus.ueberla@fau.de.
Abstract
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.
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) infectedpatients. 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.
Authors: Ali Manouchehrinia; Radu Tanasescu; Huner Kareem; Oltita P Jerca; Fouzia Jabeen; Rachelle Shafei; Judith Breuer; Keith Neal; William Irving; Cris S Constantinescu Journal: J Neurovirol Date: 2017-09-11 Impact factor: 2.643