The results demonstrate an association between EBV reactivation and disease activity in MS patients over time, and suggest that EBV might play an indirect role in MS as an activator of the underlying disease process.

In this study, the prevalence and reactivity of anti-Epstein-Barr virus (EBV) antibodies were investigated in 107 patients with multiple sclerosis (MS) in comparison to age- and gender-matched healthy controls from a north German state. We found a significant 100% EBV-seropositivity and a significant lack of primary EBV infections in the MS group, indicating that all MS patients are infected with EBV before the development of MS. Although there were no differences in reactivities of EBV-specific anti-early antigen (EA)-immunoglobulin G (IgG), -IgM, and -IgA antibodies between each group, MS patients had significant lower anti-Epstein-Barr nuclear antigen (EBNA)1-IgG antibody titers as a possible serological sign for a defective control of the persistent latent EBV carrier state and EBV reactivations. Longitudinal studies of MS patients are necessary to further determine the implications of EBV reactivations on the course and disease activity of MS.

Several lines of evidence have supported the role of immunological mechanisms in the pathogenesis of multiple sclerosis (MS) and new immunomodulatory strategies for its treatment, e.g. subcutaneous application of interferon (IFN)-beta, have emerged. We investigated the ability of peripheral blood mononuclear cells (PBMC) in 21 consecutive patients with clinically definite MS to produce interferons and lymphokines in response to viral or mitogenic stimulation. Ten patients showed clinical signs of disease activity (acute relapse) and 11 patients were in a stable condition. Additionally, white blood count, leukocyte differentiation and lymphocyte subtyping were performed. A group of age-related healthy blood donors served as control (n=20). There was no difference between patients and controls in the production of IFN-gamma, tumor necrosis factor (TNF)-alpha and soluble interleukin (IL)-2 receptor. IFN-alpha and IFN-beta responsiveness, however, was significantly lower in patients with stable disease than in patients with active disease and controls (p<0.001). Furthermore, secretion of IL-2 after stimulation was significantly diminished in both patient groups as compared to the control group (p<0.01). Analysis of T-cell subsets revealed a significantly lower amount of CD8+ T-cells in patients with stable disease, leading to a significantly higher CD4/CD8 ratio in this group as compared to patients with active disease. Our study depicted an IL-2 deficiency in MS patients which is shared with other autoimmune diseases. In addition, our findings suggest that the ability to produce type-I IFNs, IFN-alpha and IFN-beta, is primarily impaired in MS patients and changes in correlation to the course of disease activity.