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Gut 55:478-484 doi:10.1136/gut.2005.069385
  • Coeliac disease

Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease

  1. W Dieterich1,
  2. B Esslinger1,
  3. D Trapp1,
  4. E Hahn1,
  5. T Huff2,
  6. W Seilmeier3,
  7. H Wieser3,
  8. D Schuppan4
  1. 1Department of Medicine I, University of Erlangen-Nuernberg, Germany
  2. 2Department of Biochemistry, University of Erlangen-Nuernberg, Germany
  3. 3German Research Centre of Food Chemistry, Garching, Germany
  4. 4Department of Medicine I, University of Erlangen-Nuernberg, Germany, and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to:
    Dr W Dieterich
    Department of Medicine I, University of Erlangen-Nuernberg, Glueckstrasse 10, Hofgebäude Labor Prof Schuppan, Erlangen 91054, Germany; walburga.dieterich{at}med1.imed.uni-erlangen.de
  • Accepted 20 September 2005
  • Revised 23 August 2005
  • Published Online First 27 September 2005

Abstract

Background and aims: Intestinal inflammation in coeliac disease is driven by the gluten fraction of wheat proteins. Deamidation or cross linking of gluten peptides by tissue transglutaminase (tTG), the coeliac disease autoantigen, creates potent T cell stimulatory peptides. Therefore, our aim was to identify the reaction patterns of gluten peptides, intestinal extracellular matrix proteins, and tTG.

Methods: tTG activity was analysed by incorporation of monodansyl cadaverine into gliadins. Fluorescence labelled tTG reactive short gliadin peptides were used to demonstrate their deamidation and explore their cross linking patterns with tTG itself or extracellular matrix proteins. Patient sera and controls were checked for autoantibodies to matrix proteins.

Results: Gliadins α1–α11, γ1–γ6, ω1–ω3, and ω5 were substrates for tTG. tTG catalysed the cross linking of gliadin peptides with interstitial collagen types I, III, and VI. Coeliac patients showed increased antibody titres against the collagens I, III, V, and VI.

Conclusions: tTG formed high molecular weight complexes with all tested gliadins. As all tested gliadins were substrates for tTG, the tTG catalysed modifications were not restricted to single gliadin types and epitopes. Furthermore, haptenisation and long term immobilisation of gliadin peptides by tTG catalysed binding to abundant extracellular matrix proteins could be instrumental in the perpetuation of intestinal inflammation and some associated autoimmune diseases in coeliac disease.

Footnotes

  • Published online first 27 September 2005

  • This study was supported by grants Schu 646/11-3 from the Deutsche Forschungsgesellschaft and by grants of the commission of the European Communities, Coeliac EU-cluster program “Quality of Life and Management of Living Resources, QLRT-1999-00037”.

  • Conflict of interest: None declared.