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From the Center for Neurologic Diseases, Department of Neurology (P.L.D.J., D.A.H.), and Channing Laboratory, Department of Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston; Harvard Medical School/Partners Healthcare Center for Genetics and Genomics (P.L.D.J., D.A.H.); Broad Institute (P.L.D.J., J.D.R., D.A.H.), Massachusetts Institute of Technology and Harvard University, Cambridge; Departments of Epidemiology (K.C.S., A.A.) and Nutrition (K.L.M., A.A.), Harvard School of Public Health, Cambridge, MA; and University of Montreal (J.D.R.), Montreal Heart Institute, Montreal, Quebec, Canada.
* To whom correspondence should be addressed. E-mail: aascheri{at}hsph.harvard.edu.
ABSTRACT
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.
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