Primary infection with the Epstein-Barr virus and risk of multiple sclerosis

Abstract

To determine whether multiple sclerosis (MS) risk increases following primary infection with the Epstein-Barr virus (EBV), we conducted a nested case-control study including 305 individuals who developed MS and 610 matched controls selected among the >8 million active-duty military personnel whose serum has been stored in the Department of Defense Serum Repository. Time of EBV infection was determined by measuring antibody titers in serial serum samples collected before MS onset among cases, and on matched dates among controls. Ten (3.3%) cases and 32 (5.2%) controls were initially EBV negative. All of the 10 EBV-negative cases became EBV positive before MS onset; in contrast, only 35.7% (n = 10) of the 28 controls with follow-up samples seroconverted (exact p value = 0.0008). We conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection.

Figure 1

Time of EBV seroconversion and MS onset in the 10 cases who were seronegative at baseline. The vertical lines within each bar represent the time of blood collections after the initial sample, which was taken at time zero for each individual. The arrows and bar darkening mark the time of the first EBV positive serum. The black circles are drawn at the time of MS onset.