Human interferon regulatory factor 5 homologous epitopes of Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis induce a specific humoral and cellular immune response in multiple sclerosis patients

Background: A large number of reports indicate the association of Epstein-Barr virus (EBV), and Mycobacterium avium subsp. paratuberculosis (MAP) with multiple sclerosis (MS). Objective: To gain a better understanding of the role of these two pathogens, we investigated the host response induced by selected antigenic peptides. Methods: We examined both humoral and cell-mediated responses against peptides deriving from EBV tegument protein BOLF1, the MAP-4027 and the human interferon regulatory factor 5 (IRF5424-434) homolog in several MS patients and healthy controls (HCs). Results: Antibodies against these peptides were highly prevalent in MS patients compared to HCs. Concerning MS patients, BOLF1305-320, MAP-402718-32 and IRF5424-434 peptides were able to induce mainly Th1-related cytokines secretion, whereas Th2-related cytokines were down-regulated. Flow cytometry analyses performed on a subset of MS patients highlighted that these peptides were capable of inducing the release of pro-inflammatory cytokines: IFN-γ and TNF-α by CD4⁺ and CD8⁺ T lymphocytes, and IL-6 and TNF-α by CD14⁺ monocyte cells. Conclusion: Our data demonstrated that both EBV and MAP epitopes elicit a consistent humoral response in MS patients compared to HCs, and that the aforementioned peptides are able to induce a T-cell-mediated response that is MS correlated.