EBV and Risk of MS
Abstract & Commentary
Source: Ascherio A, et al. Epstein-Barr virus antibodies and risk of multiple sclerosis. JAMA. 2001;286:3083-3088.
From more than 60,000 nurses participating in the Nurses Health Study by the Harvard School of Public Health, Ascherio and colleagues identified 144 women with probable or definite multiple sclerosis (MS) and 288 matched controls, all of whom had provided blood samples. Of these, 18 cases of MS were documented to have serum collected before the onset of MS. When their serum was tested for antibodies against cytomegalovirus (CMV) and Epstein-Barr virus (EBV), they were found to have significantly higher antibody titers to EBV proteins EBNA-2 and EBNA-1 compared to controls (P = 0.01 and 0.02, respectively). Weaker elevations in antibodies against EBV were seen in 126 cases of MS with blood collected after disease onset.
Wandinger and colleagues determined the prevalence of antibodies and PCR DNA positivity to EBV, CMV, HSV-1, and HSV-2 in 108 MS patients and 163 healthy controls (Wandinger K, et al. Neurology. 2000;55:178-184). Serial monthly blood testing indicated frequent EBV reactivation in MS, particularly in those MS patients with more active disease (50-100%), compared to controls (17%).
Commentary
The association of human herpes viruses, including EBV (HHV-5), and HHV-6 with MS has been discussed previously (Apatoff BR. Neurology Alert. 1999; 17:57-58). Indeed, demyelinating events have been reported in the literature with acute EBV infection and other herpes viruses over the years. The study by Ascherio et al, however, is suboptimal as a prospective study for MS because most serum samples were collected from subjects older than 40-60 years of age, when MS typically presents between the ages of 20-40. One difficulty with establishing a disease association for EBV is that this ubiquitous virus is found in more than 95% of healthy people by adulthood, with most persons being asymptomatically infected. Similarly, other systemic autoimmune disease (eg, rheumatoid arthritis) or nonspecific stress has been associated with EBV reactivation and possibly increased antibody titers. While a causal etiology for EBV and MS cannot be made from the above studies, its association with MS and a variety of other lymphoproliferative or autoimmune disease remains of interest. Whether viral activation is a primary process in MS, or just a secondary phenomenon occurring with immune activation, will be important in the success of future therapeutic strategies. —Brian R. Apatoff, MD, PhD. Dr. Apatoff, Associate Professor of Neurology, New York Presbyterian Hospital- Cornell Campus, is Assistant Editor of Neurology Alert.
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