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

Mult Scler. 2015 Dec;21(14):1823-32. doi: 10.1177/1352458515576984. Epub 2015 Mar 31.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / blood*
  • Child
  • Disease Susceptibility
  • Female
  • HIV Infections / blood
  • Herpes Zoster / blood*
  • Herpesvirus 3, Human / immunology*
  • 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

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Immunologic Factors
  • Natalizumab