Innate and adaptive anti-viral immune responses in MS patients treated with interferon-beta

Abstract

Background Interferon-beta (IFN-b) has both immuno-modulating and anti-viral effects. In a longitudinal study of multiple sclerosis (MS) patients undergoing interferon-beta therapy, we have performed a comprehensive study of factors in the innate and adaptive immune response to the two types of virus associated with MS: human endogenous retroviruses (HERVs), and herpesviruses. Materials and methods Anti-viral antibodies towards HERVs and herpesviruses were assayed using TRIFMA or ELISA. Cytokine profiling was performed using the Luminex-system. Factors in the lectin complement activation pathway were assayed using TRIFMA. Results We demonstrate significant decreases in anti-Envelope antibody reactivity for the two closely related Gammaretroviral HERVs, HERV-H and HERV-W, as a consequence of IFN-b therapy, closely linked to efficacy of therapy/low disease activity. We also found strong indications of a protective effect of high levels of two components in the innate pathogen-associated molecular pattern recognition: mannan-binding lectin (MBL), and MASP-3. Serum levels of typical Th1- and Th2- related, MSrelevant cytokines were also monitored. We found no overall changes in Th1/Th2 ratios. Conclusions Our results support that IFN-b exerts effects on immune response to HERV-H/HERV-W, and that this antiviral response may play a role in MS development. Components in the immune response to HERVs have potential as biomarkers for disease activity.