Munger et al. Anti-Epstein-Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel. Mult Scler. 2011 Oct;17(10):1185-93.
BACKGROUND: Elevated Epstein-Barr virus (EBV) antibody titers are risk factors for multiple sclerosis (MS), but the strength and consistency of this association are not well characterized.
OBJECTIVES: The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness ofEBV nuclear antigen (EBNA) antibodies as a marker for MS.
METHODS: We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks.
RESULTS: MS risk increased with increasing titers of anti-EBNA complex (p < 10(-9)) and anti-EBNA-1 (p = 5.8 × 10(-9)) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95% confidence interval [CI] 9.6-136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95% CI 2.6-23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the receiver operating characteristic (ROC) curves were 0.67 for EBNA complex and 0.65 for EBNA-1.
CONCLUSIONS: Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score.
"This study suggests that the antibody levels to EBV are not linked to the levels of vitamin D. The problem with this study is that the average vD levels were not that low. In addition, vD levels are cyclical across the year being highest at the end of summer and lowest at the end of winter. Therefore I am not convinced that there is no association between these two variables. We need more data. However, if the anti-EBNA-1 levels and vD levels are truly independent of each other then we need to explain their role in the pathogenesis of MS."