RETRACTED: Multiple sclerosis and Epstein-Barr virus (Retracted Article. See vol 293, pg 2466, 2005)

Context Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. Objective To determine whether antibodies to EBV are elevated before the onset of MS. Design, Setting, and Population Nested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n=83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Main Outcome Measures Antibodies including IgA against EBV viral capsid antigen (VCA) and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. Results The average time between blood collection and MS onset was 4 years. The strongest predictors of MS were serum levels of IgG antibodies to VCA or EBNA complex. The risk of MS increased monotonically with these antibody titers; relative risk (RR) in persons in the highest category of VCA (greater than or equal to2560) compared with those in the lowest (less than or equal to160) was 19.7 (95% confidence interval [CI], 2.2-174; P for trend =.004). For EBNA complex titers, the RR for those in the highest category (greater than or equal to1280) was 33.9 (95% CI, 4.1-283; P for trend <.001) vs those in the lowest category (<= 40). Similarly strong positive associations between EBV antibodies and risk of MS were already present in samples collected 5 or more years before MS onset. No association was found between cytomegalovirus antibodies and MS. Conclusion These results suggest a relationship between EBV infection and development of MS.