Integrating risk factors: HLA-DRB1*1501 and Epstein-Barr virus in multiple sclerosis

Neurology. 2008 Mar 25;70(13 Pt 2):1113-8. doi: 10.1212/01.wnl.0000294325.63006.f8. Epub 2008 Feb 13.


Background: Individuals with high levels of antibodies to the Epstein-Barr virus nuclear antigen 1 (EBNA-1) have an increased risk of developing multiple sclerosis (MS), but this association could be confounded by genetic susceptibility.

Methods: We conducted a nested case-control study including 148 women with MS (18 with blood collected before disease onset) and 296 age-matched healthy women to determine whether the human leukocyte antigen (HLA) DRB1*1501 allele (DR15) and anti-Epstein-Barr virus (anti-EBV) antibody titers are independent risk factors for MS.

Results: The association between anti-EBNA-1 antibody titers and MS risk was not affected by adjustment for DR15 and was similar in DR15-positive and DR15-negative women. The relative risk of MS among DR15-positive women with elevated (>1:320) anti-EBNA-1 titers was ninefold higher than that of DR15-negative women with low (<1:80) anti-EBNA-1 titers.

Conclusions: Anti-Epstein-Barr virus nuclear antigen 1 (anti-EBNA-1) antibody titers are a risk factor for multiple sclerosis (MS), independently from the DR15 allele. Carriers of the DR15 allele with elevated anti-EBNA-1 antibody titers may have a markedly increased risk of MS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies / analysis
  • Antibodies / blood
  • Antibodies / immunology
  • Biomarkers / analysis
  • Biomarkers / blood
  • Case-Control Studies
  • Comorbidity
  • Epstein-Barr Virus Infections / epidemiology*
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Nuclear Antigens / immunology
  • Female
  • Gene Frequency / genetics
  • Gene Frequency / immunology
  • Genetic Predisposition to Disease / epidemiology
  • Genotype
  • HLA-DR Antigens / blood*
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology*
  • HLA-DRB1 Chains
  • Herpesvirus 4, Human / immunology
  • Heterozygote
  • Humans
  • Middle Aged
  • Multiple Sclerosis / epidemiology*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology*
  • Risk Factors


  • Antibodies
  • Biomarkers
  • Epstein-Barr Virus Nuclear Antigens
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • EBV-encoded nuclear antigen 1