The toxicity of high molecular weight glutenin subunits of wheat to patients with coeliac disease

Eur J Gastroenterol Hepatol. 2006 May;18(5):483-91. doi: 10.1097/00042737-200605000-00005.


Objectives: The ability of the gliadin fraction of wheat gluten to exacerbate coeliac disease is well documented. We investigated the possible toxicity of high molecular weight glutenin subunits (HMW-GS) in coeliac disease in vitro using gluten-sensitive T cells, and in vivo with challenge studies in patient volunteers.

Methods: A mixture of four HMW-GS was chemically separated from wheat flour and checked for purity by HPLC, SDS-PAGE and ELISA. T-cell lines, grown up from small intestinal biopsies from coeliac patients (n=17), were tested for their reactivity to HMW-GS. Adults with coeliac disease and who were on a gluten-free diet (n=3) underwent in-vivo challenges with HMW-GS. Duodenal biopsies, taken prior to the challenge and at intervals up to 6 h afterwards, were assessed for morphology, intra-epithelial lymphocyte count, and interleukin 15 (IL-15) expression, by immunohistochemistry.

Results: T-cell lines from 11 of 17 patients were stimulated by HMW-GS. There was a significant change in small intestinal morphology 4 h after commencing infusions with HMW-GS in all three subjects. For example villus height to crypt depth ratios were reduced in the three patients from 3.0+/-0.5 to 1.29+/-0.2, 2.53+/-0.7 to 0.81+/-0.6 and 3.0+/-0.7 to 1.85+/-0.3, P<0.0001 in all cases. There was increased expression of IL-15 in the small intestine from 2 h after the HMW-GS challenges.

Conclusion: Mixed HMW-GS stimulate T-cell lines from some coeliac patients and exacerbate coeliac disease in vivo, inducing expression, within 2 h, of IL-15. This suggests an innate immune response to these proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Celiac Disease / immunology
  • Celiac Disease / pathology*
  • Cell Line
  • Diet, Protein-Restricted
  • Epitopes / immunology
  • Female
  • Glutens / administration & dosage
  • Glutens / adverse effects*
  • Glutens / immunology
  • Glutens / isolation & purification
  • Humans
  • Immunohistochemistry / methods
  • Interferon-gamma / immunology
  • Interleukin-15 / analysis
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Intestine, Small / immunology
  • Intestine, Small / pathology
  • Male
  • Middle Aged
  • Molecular Weight
  • T-Lymphocytes / immunology
  • Triticum / chemistry*


  • Epitopes
  • Interleukin-15
  • Glutens
  • Interferon-gamma
  • glutenin