Epstein-Barr Virus Linked to Multiple Sclerosis

Laurie Barclay, MD

March 25, 2003 — Epstein-Barr virus (EBV) is associated with increased risk of multiple sclerosis (MS), according to the results of a large, nested, case-control study published in the March 26 issue of The Journal of the American Medical Association.

"The baseline geometric mean serum antibody titers to EBV were consistently higher among individuals who later developed MS than among their matched controls," write Lynn I. Levin, PhD, MPH, from the U.S. Army Physical Disability Agency in Washington, D.C., and colleagues. "Similarly strong positive associations between EBV antibodies and risk of MS were already present in samples collected five or more years before MS onset."

Using the Department of Defense Serum Repository of blood samples collected between 1988 and 2000 from more than 3 million U.S. military personnel, the investigators identified 83 individuals granted temporary or permanent disability because of MS. Two controls for each of these cases were matched by age, sex, race, ethnicity, and dates of blood sample collection. The mean length of time between blood collection and onset of MS was four years.

The strongest predictors of MS were serum levels of IgG antibodies to EBV viral capsid antigen (VCA) or nuclear antigen (EBNA) complex. Rising levels of these antibodies correlated linearly with increasing risk of MS. Compared with those in the group of lowest VCA titers (/= 2,560) was 19.7 (95% confidence interval [CI], 2.2 - 174; P for trend = .004). Compared with those who had EBNA complex titers /= 1,280 was 33.9 (95% CI, 4.1 - 283; P for trend <.001.

Samples collected five years or more before MS onset also showed strong positive associations between EBV antibodies and risk of MS. No relationship was detected between cytomegalovirus antibodies and risk of MS.

According to the authors, these findings suggest that "the increased antibody response to EBV occurs early in relation to the pathological process that leads to demyelination and clinical disease," and that "there is a long lag time between infection with EBV and occurrence of MS.... These results support a role for EBV in the etiology of MS."

JAMA. 2003;289:1533-1536

Reviewed by Gary D. Vogin, MD