A Prospective Study
http://jama.ama-assn.org/issues/v286n24/abs/joc11194.html
JAMA. 2001;286:3083-3088
Alberto Ascherio, MD, DrPH; Kassandra
L. Munger, MSc; Evelyne T. Lennette, PhD; Donna Spiegelman, ScD; Miguel
A. Hernán, MD, DrPH; Michael J. Olek, DO; Susan E. Hankinson, ScD;
David J. Hunter, ScD
Context
Epidemiological studies suggest an
association between infection with Epstein-Barr virus (EBV) and risk of
multiple sclerosis (MS).
Objective
To determine whether elevation in
serum antibody titers to EBV viral capsid antigen (VCA), nuclear antigens
(EBNA, EBNA-1, and EBNA-2), and diffuse and restricted early antigen (EA-D
and EA-R) as well as to cytomegalovirus (CMV) precede the occurrence of
MS.
Design, Setting, and Subjects
Prospective, nested case-control
study. Of 62 439 women participating in the Nurses' Health Study (aged
30-55 years in 1976) and Nurses' Health Study II (aged 25-42 years in 1989)
who gave blood samples in 1989-1990 and 1996-1999, respectively, and were
followed up through 1999, 144 women with definite or probable MS and 288
healthy age-matched controls were included in the analysis.
Main Outcome Measure
Serum antibody titers to the specific
EBV and CMV antigens, compared between cases and controls.
Results
We documented 18 cases of MS with
blood collected before disease onset. Compared with their matched controls,
these women had higher serum geometric mean titers (GMTs) of antibodies
to EBV but not CMV. Elevations were significant for antibodies to EBNA-1
(GMT, 515 vs 203; P = .03), EBNA-2 (GMT, 91 vs 40; P = .01), and EA-D (15.9
vs 5.9; P = .04). The strongest association was found for antibodies to
EBNA-2; a 4-fold difference in titers was associated with a relative risk
(RR) of MS of 3.9 (95% confidence interval [CI], 1.1-13.7). The corresponding
RRs were 1.6 (95% CI, 0.7-3.7) for VCA, 2.5 (95% CI, 1.0-6.3) for EBNA,
1.8 (95% CI, 1.0-3.1) for EA-D, and 1.0 (95% CI, 0.6-1.7) for CMV. Significant
but generally weaker elevations in anti-EBV antibodies were also found
in analyses of 126 cases of MS with blood collected after disease onset
and their matched controls.
Conclusions
Our results support a role of EBV
in the etiology of MS.
© 2001 American Medical Association