Crosslinking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease

Walburga Dieterich ^1*, Birgit Esslinger ¹, Dagmar Trapp ¹, Eckhart Hahn ¹, Thomas Huff ², Werner Seilmeier ³, Herbert Wieser ³ and Detlef Schuppan ⁴

¹ Department of Medicine I, University of Erlangen-Nuernberg, Germany
² Department of Biochemistry, University of Erlangen-Nuernberg, Germany
³ German Research Centre of Food Chemistry, Garching, Germany
⁴ Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States

^* To whom correspondence should be addressed. E-mail: walburga.dieterich{at}med1.imed.uni-erlangen.de.

Accepted 20 September 2005

Abstract

Background & Aims: Intestinal inflammation in coeliac disease is driven by the gluten fraction of wheat proteins. Deamidation or crosslinking of gluten peptides by tissue transglutaminase (tTG), the coeliac disease autoantigen, creates potent T cell stimulatory peptides. Therefore, we aimed at identifying the reaction patterns of gluten peptides, intestinal extracellular matrix proteins and tTG.

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

Results: Gliadins 1-11, 1- 6, 1-3, and 5 were substrates for tTG. tTG catalyzed the crosslinking of gliadin peptides with interstitial collagens type I, III and VI. Coeliac patients showed increased antibody titers against the collagens I, III, V and VI.

Conclusions: tTG forms high molecular weight complexes with all tested gliadins. Since all tested gliadins are substrates for tTG, the tTG-catalyzed modifications are not restricted to single gliadin types and epitopes. Furthermore, haptenization and long-term immobilization of gliadin peptides by tTG-catalyzed binding to abundant extracellular matrix proteins could be instrumental in the perpetuation of intestinal inflammation and some associated autoimmune diseases in coeliac disease.

Keywords: coeliac disease, collagens, tissue transglutaminase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Digest

Robin Spiller and Alastair Watson
Gut 2006 55: 437. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Iismaa, S. E., Mearns, B. M., Lorand, L., Graham, R. M. (2009). Transglutaminases and Disease: Lessons From Genetically Engineered Mouse Models and Inherited Disorders. Physiol. Rev. 89: 991-1023 [Abstract] [Full Text]