It has been suggested that the Epstein-Barr virus (EBV) plays a role in the etiology of multiple sclerosis (MS), but individual epidemiologic studies have been inconclusive, in part because of the high prevalence of previous infection among individuals without MS. We conducted a systematic review of case-control studies comparing EBV serology in MS patients and controls. Eight published investigations were identified, including a total of 1,005 cases and 1,060 controls. The summary odds ratio of MS comparing EBV seropositive individuals with EBV seronegative individuals was 13.5 (95% CI = 6.3-31.4). The strength and consistency of this association and the high sensitivity and specificity of EBV serology suggest that these results are not readily explained by an aspecific immune activation among MS patients. These findings support a role of EBV in the etiology of MS.
Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.