EBV-specific immune responses in patients with multiple sclerosis responding to IFNβ therapy

Background: Symptomatic primary infection with the human gamma-herpesvirus Epstein-Barr virus (EBV) and elevated immune responses to EBV are associated with the development and progression of multiple sclerosis (MS). Interferon-beta (IFN beta), first-line treatment for relapse-onset MS, exhibits complex immunoregulatory and antiviral activities. Objective: To determine EBV-specific immune responses in patients with MS during IFN beta therapy. Methods: We evaluated cellular and humoral immune responses to EBV- and human cytomegalovirus (HCMV)-encoded antigens in patients with MS before and 1 year after IFN beta treatment by ELISA and flow cytometry. Twenty-eight patients with MS who showed a clinical response to IFN beta as defined by the absence of relapses and lack of progression on the Expanded Disability Status Scale score during the first 2 years of treatment were included. Results: Clinically effective IFN beta-therapy was associated with a downregulation of proliferative T cell responses to the latent EBV nuclear antigen-1 (EBNA1). EBNA1-specific IgG responses as well as cellular and humoral immune responses to MHC class I restricted EBV antigens expressed during lytic replication and viral B cell transformation were similar before and after IFN beta therapy. Although HCMV-specific IgG levels slightly decreased, proliferative T-cell responses towards HCMV antigens remained unchanged during IFN beta therapy. Conclusion: Clinically effective IFN beta therapy is associated with a reduction of proliferative T-cell responses to EBNA1.