title: Immune response induced by Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis peptides in current and past infectious mononucleosis: a risk for multiple sclerosis?
abstract: OBJECTIVE
  Infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) has been associated with increased risk of multiple sclerosis (MS). However, the mechanism linking these pathologies is unclear. Different reports indicate the association of EBV, and recently Mycobacterium avium subsp. paratuberculosis (MAP), with MS. For a better understanding of the role of these pathogens, the host response induced by selected antigenic peptides in subjects with a history of IM that significantly increases the risk of MS was investigated.
  
  
  METHODS
  Both humoral and cell-mediated response against peptides able to induce a specific immune activation in MS patients deriving from lytic and latent EBV antigens BOLF1(305-320), EBNA1(400-413), from MAP MAP_4027(18-32), MAP_0106c(121-132) and from human proteins IRF5(424-434) and MBP(85-98) in subjects with current and past IM were examined.
  
  
  RESULTS
  EBNA1 and MAP_0106c peptides were able to induce a humoral immune response in subjects with a history of clinical IM in an independent manner. Moreover, these peptides were capable of inducing pro-inflammatory cytokine interferon γ by CD4+ and CD8+ T lymphocytes and interleukin 6 and tumour necrosis factor α by CD14+ monocyte cells.
  
  
  CONCLUSIONS
  Our results highlight that EBV and MAP may be involved independently in the same causal process leading to MS in subjects with a history of IM.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mameli
authors.affiliation: Unit of Infectious Diseases, University of Sassari, Sassari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Madeddu
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cossu
authors.affiliation: Department of Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Galleri
authors.affiliation: Department of Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Manetti
authors.affiliation: Unit of Infectious Diseases, University of Sassari, Sassari, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Babudieri
authors.affiliation: Unit of Infectious Diseases, University of Sassari, Sassari, Italy.
authors.forename: M Stella
authors.initials: MS
authors.lastname: Mura
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: L A
authors.initials: LA
authors.lastname: Sechi
mesh_terms: D000328:Adult; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000150:complications / Q000276:immunology*; D008297:Male; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology*; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D055815:Young Adult
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D010455:Peptides
keywords: Epstein-Barr virus; Mycobacterium avium subsp. paratuberculosis; antigen-specific T-cell stimulation; cytokines; humoral response; infectious mononucleosis