title: Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis.
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.
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, Germany.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Kohlmann
authors.affiliation: Department of Neurology, Sankt Josef-Hospital, Ruhr-University Bochum, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Salmen
authors.affiliation: Department of Neurology, Sankt Josef-Hospital, Ruhr-University Bochum, Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chan
authors.affiliation: Institute of Laboratory and Transfusion Medicine, Heart and Diabetes Centre North Rhine-Westphalia, Ruhr-University Bochum, Bad Oeynhausen, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Knabbe
authors.affiliation: Institute of Laboratory and Transfusion Medicine, Heart and Diabetes Centre North Rhine-Westphalia, Ruhr-University Bochum, Bad Oeynhausen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Diekmann
authors.affiliation: German Competence Network for HIV/AIDS; Department of Dermatology, Venerology and Allergology; Sankt Josef-Hospital; Ruhr-University Bochum; Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Brockmeyer
authors.affiliation: German Competence Network for HIV/AIDS; Department of Dermatology, Venerology and Allergology; Sankt Josef-Hospital; Ruhr-University Bochum; Germany.
authors.forename: Adriane
authors.initials: A
authors.lastname: Skaletz-Rorowski
authors.affiliation: Clinical Trials Center (ZKS), Cologne, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Michalik
authors.affiliation: Department of Neurology, Sankt Josef-Hospital, Ruhr-University Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: 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.
authors.forename: Klaus
authors.initials: K
authors.lastname: Überla
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D004198:Disease Susceptibility; D005260:Female; D015658:HIV Infections / Q000097:blood; D006562:Herpes Zoster / Q000097:blood*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D007155:Immunologic Factors / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy*; D000069442:Natalizumab / Q000009:adverse effects*; D014775:Virus Activation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007155:Immunologic Factors; D000069442:Natalizumab
keywords: Adverse events; JC virus; antibodies; autoimmune disease; blood donors; herpes zoster; human immunodeficiency virus; immunosuppression; multiple sclerosis; natalizumab; neurotropic virus; risk factors; subclinical reactivation; varicella-zoster virus; virus reactivation