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Does cross-reactivity between mycobacterium avium paratuberculosis and human intestinal antigens characterize Crohn's

Dimitrios Polymeros1, Dimitrios P Bogdanos, Richard Day

  • 1University College London, London, United Kindgom.

Gastroenterology
|July 13, 2006
PubMed
Abstract

Insights

Crohn's disease patients exhibit cross-reactive antibodies targeting Mycobacterium avium paratuberculosis (MAP) and intestinal proteins. Gastrointestinal glutathione peroxidase is identified as a novel autoantigen in Crohn's disease.

Area of Science:

  • Immunology
  • Gastroenterology
  • Microbiology

Background:

  • Most Crohn's disease (CD) patients display seroreactivity to Mycobacterium avium paratuberculosis (MAP).
  • This suggests a potential pathogenic role for MAP in CD development.
  • Molecular mimicry between MAP and intestinal proteins may drive cross-reactive immunity.

Purpose of the Study:

  • To identify amino acid similarities between MAP and human intestinal proteins.
  • To investigate these similarities as potential targets for cross-reactive immunity in CD.
  • To explore the role of gastrointestinal glutathione peroxidase as a novel autoantigen.

Main Methods:

  • Synthesized 53 peptides representing 23 MAP/human intestinal mimic sets with maximal homology.
  • Assessed immunologic cross-reactivity using enzyme-linked immunosorbent assay (ELISA).
  • Tested samples from 50 CD patients, 50 ulcerative colitis patients, and 38 healthy controls.

Main Results:

  • MAP/self-reactivity was found in 42% of CD patients but was rare in controls.
  • Significant double-reactivity was observed against MAP glycosyl transferase d/human gastrointestinal glutathione peroxidase (GPg) homologues in 30% of CD patients.
  • MAP alkylohydroperoxidase C/human tumor overexpressed protein homologues showed double-reactivity in 20% of CD patients.
  • Inhibition studies confirmed cross-reactivity, and 3D modeling suggested GPg exposure.
  • Higher antibody affinity for MAP mimics indicated prior reactivity to mycobacterial sequences.

Conclusions:

  • MAP/self-mimics are targets of cross-reactive antibody responses in Crohn's disease patients.
  • Gastrointestinal glutathione peroxidase (GPg) is identified as a novel autoantigen in CD.
  • These findings provide insights into the autoimmune mechanisms underlying Crohn's disease.

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