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

Mult Scler. 2015 Jul;21(8):984-95. doi: 10.1177/1352458514557304. Epub 2014 Nov 12.

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.

Keywords: Epstein-Barr virus; Mycobacterium avium subsp. paratuberculosis; antigen-specific T-cell stimulation; cytokines; humoral response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies / analysis
  • Antigens / immunology
  • Binding, Competitive
  • Cytokines / metabolism
  • Epitopes
  • Female
  • Flow Cytometry
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunity, Cellular / immunology*
  • Immunity, Humoral / immunology*
  • In Vitro Techniques
  • Interferon Regulatory Factors / immunology*
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / microbiology
  • Multiple Sclerosis / virology
  • Mycobacterium avium subsp. paratuberculosis / immunology*
  • Peptides / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism

Substances

  • Antibodies
  • Antigens
  • Cytokines
  • Epitopes
  • IRF5 protein, human
  • Interferon Regulatory Factors
  • Peptides