Epstein-Barr virus and multiple sclerosis: interaction with HLA

Genes Immun. 2012 Jan;13(1):14-20. doi: 10.1038/gene.2011.42. Epub 2011 Jul 21.


Epstein-Barr virus (EBV) infection, history of infectious mononucleosis (IM) and HLA-A and DRB1 have all been proposed as risk factors for multiple sclerosis (MS). Our aim was to analyse possible interactions between antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA1) or EBNA1 fragments, presence of DRB1*15 and absence of A*02. The study population includes newly diagnosed cases and matched controls. Interaction on the additive scale was calculated using attributable proportion due to interaction (AP), which is the proportion of the incidence among individuals exposed to two interacting factors that is attributable to the interaction per se. IM showed association with MS, odds ratio (OR)=1.89 (1.45-2.48% confidence interval (CI)), as did raised EBNA1 IgG OR=1.74 (1.38-2.18 95%CI). All EBNA1 fragment IgGs were associated with MS risk. However, EBNA1 fragment 385-420 IgG levels were more strongly associated to MS than total EBNA1 IgG, OR=3.60 (2.75-4.72 95%CI), and also interacted with both DRB1*15 and absence of A*02, AP 0.60 (0.45-0.76 95%CI) and AP 0.39 (0.18-0.61 95%CI), respectively. The observed interaction between HLA class I and II genotype and reactivity to EBV-related epitopes suggest that the mechanism through which HLA genes influence the risk of MS may, at least in part, involve the immune control of EBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Epstein-Barr Virus Nuclear Antigens / immunology
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • HLA-DRB1 Chains / genetics
  • HLA-DRB1 Chains / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunoglobulin G / immunology
  • Infectious Mononucleosis / genetics
  • Infectious Mononucleosis / immunology
  • Infectious Mononucleosis / virology
  • Middle Aged
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / virology
  • Risk Factors
  • Smoking / adverse effects
  • Young Adult


  • Epstein-Barr Virus Nuclear Antigens
  • HLA Antigens
  • HLA-A Antigens
  • HLA-DRB1 Chains
  • Immunoglobulin G