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.


CONCLUSIONS
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.
Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari, Italy.
Davide
D
Cossu
Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari, Italy.
Giuseppe
G
Mameli
Dipartimento di Medicina Clinica e Sperimentale, Università di Sassari, Italy.
Grazia
G
Galleri
Centro Sclerosi Multipla, Dipartimento di Sanità Pubblica Medicina Clinica e Molecolare, Università di Cagliari, Italy.
Eleonora
E
Cocco
Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari, Italy.
Speranza
S
Masala
Centro Sclerosi Multipla, Dipartimento di Sanità Pubblica Medicina Clinica e Molecolare, Università di Cagliari, Italy.
Jessica
J
Frau
Centro Sclerosi Multipla, Dipartimento di Sanità Pubblica Medicina Clinica e Molecolare, Università di Cagliari, Italy.
Maria Giovanna
MG
Marrosu
Dipartimento di Medicina Clinica e Sperimentale, Università di Sassari, Italy.
Roberto
R
Manetti
Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università di Sassari, Italy sechila@uniss.it.
Leonardo Antonio
LA
Sechi
D000328:Adult; D000906:Antibodies / Q000032:analysis; D000941:Antigens / Q000276:immunology; D001667:Binding, Competitive; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D066298:In Vitro Techniques; D050835:Interferon Regulatory Factors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D000906:Antibodies; D000941:Antigens; D016207:Cytokines; D000939:Epitopes; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D010455:Peptides
Epstein-Barr virus; Mycobacterium avium subsp. paratuberculosis; antigen-specific T-cell stimulation; cytokines; humoral response