Davide Cossu1, Giuseppe Mameli1, Grazia Galleri2, Eleonora Cocco3, Speranza Masala1, Jessica Frau3, Maria Giovanna Marrosu3, Roberto Manetti2, Leonardo Antonio Sechi4. 1. Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari, Italy. 2. Dipartimento di Medicina Clinica e Sperimentale, Università di Sassari, Italy. 3. Centro Sclerosi Multipla, Dipartimento di Sanità Pubblica Medicina Clinica e Molecolare, Università di Cagliari, Italy. 4. Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari, Italy sechila@uniss.it.
Abstract
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.
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 humaninterferon regulatory factor 5 (IRF5424-434) homolog in several MSpatients and healthy controls (HCs). RESULTS: Antibodies against these peptides were highly prevalent in MSpatients compared to HCs. Concerning MSpatients, 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 MSpatients 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 MSpatients compared to HCs, and that the aforementioned peptides are able to induce a T-cell-mediated response that is MS correlated.