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

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.