Epstein-Barr Virus Infection and Antibody Synthesis in Patients With Multiple Sclerosis

Patrick F. Bray, MD; Linda C. Bloomer, PhD; V. C. Salmon; Mark H. Bagley; Paul D. Larsen, MD \s=b\We studied infectious and immune mechanisms in demyelinating disease. The clinical diagnosis in this study of 313 consecutive cases of multiple sclerosis (MS) was based on the clinical conclusions of two or more neurologists and definite abnormalities in CSF lgG. Measurement of antibodies to six microbial agents was compared in 313 patients with MS and 406 controls in the same age range. Using a standardized immunofluorescent antibody (IFA) technique, we found a significantly higher prevalence of Epstein-Barr virus (EBV) infection and a higher level of serum viral capsid antigen IgG antibody titer in the MS population than in the controls. The MS population had a lower cytomegalovirus (CMV) infection rate and lower CMV complement fixing antibody production than controls. Except for the higher measles infection rate and antibody titer in patients with MS, data on the other viruses did not differ from controls. (Arch Neurol 1983;40:406-408) IV/Tultiple sclerosis (MS) is a chronic demyelinating CNS disease that usually affects young adults between 20 and 40 years of age. The disorder affects women slightly more often and at a younger age than men. The inci¬ dence is higher among persons living in northern Europe, the United States, and Canada (about one in 1,000). Studies of migrating popula¬ tions suggest that persons who move from high-incidence areas after ado¬ lescence carry with them the risk of their site of origin, and conversely, persons who migrate in the same direction before adolescence take on the lower incidence risk of the area to which they move. The etiology and pathogenesis remain obscure. However, like others, we have been attracted to an infec¬ tious-immune mechanism to explain the pathogenesis. This point of view derives from two consistent sets of clinical and pathologic observations. First, about 95% of patients carrying the clinical diagnosis of MS have qual¬ itative or quantitative IgG abnormali¬ ties in their CSF, and second, an increased number of lymphocytes is found in both the CSF and around the early MS demyelinating plaque. Con¬ vincing evidence for an infectious eti¬ ology has never been demonstrated because no microbial agent has been consistently recovered or visualized microscopically, nor has the disease been transmitted to laboratory ani¬ mals. Hereditary factors may also play a role in pathogenesis because the B7 and Dw2 histocompatibility antigens are overrepresented in the MS population.