title: Identification of coeliac disease triggering glutenin peptides in adults.
abstract: OBJECTIVE
  Coeliac disease affects approximately 1% of Northern American and European populations. It is caused by an inappropriate immune response to dietary gluten. Gluten comprises of two major protein fractions: gliadins and glutenins. Glutenins have recently been found to be toxic to coeliac individuals. Proliferation assays suggest in some but not all paediatric coeliac individuals there may be immunological stimulation with high molecular weight (HMW) glutenins. Less evidence pertains to low molecular weight (LMW) glutenins. The aim is to assess adaptive, T-cell driven, and innate immune response in adult coeliac individuals towards HMW glutenin peptide, glut04, and LMW glutenin peptide, glt156.
  
  
  METHODS
  Coeliac patients were recruited attending endoscopy for routine monitoring. Adaptive immune response towards glut04 and glt156 was measured by proliferation assays and measurement of interferon-γ secretion in 28 T-cell lines. The innate immune response was assessed by measurement of enterocyte cell height (ECH) in coeliac small intestinal biopsies following overnight incubation in organ culture chambers in a further nine individuals.
  
  
  RESULTS
  There were 3/28 and 2/28 positive proliferation results using gluten-sensitive T-cells with glut04 and glt156, respectively. All coeliac biopsies tested in organ culture chambers demonstrated clear reduction in ECH with peptic-tryptic digest of whole industrial gluten, glut04 and glt156 when compared to negative control ovalbumin (p < 0.005). Three individuals had both T-cell and organ culture study data. Their proliferation assays showed no stimulation of the T-cells.
  
  
  CONCLUSIONS
  This study demonstrates glutenin epitopes glut04 and glt156, while minor T-cell epitopes, are important in their ability to trigger the innate immune response.
authors.affiliation: a Gastroenterology Laboratory, Diabetes and Nutritional Sciences Division , Rayne Institute, St Thomas Hospital, King's College London , London , UK.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: Donnelly
authors.affiliation: a Gastroenterology Laboratory, Diabetes and Nutritional Sciences Division , Rayne Institute, St Thomas Hospital, King's College London , London , UK.
authors.forename: Tanja
authors.initials: T
authors.lastname: Šuligoj
authors.affiliation: a Gastroenterology Laboratory, Diabetes and Nutritional Sciences Division , Rayne Institute, St Thomas Hospital, King's College London , London , UK.
authors.forename: H Julia
authors.initials: HJ
authors.lastname: Ellis
authors.affiliation: a Gastroenterology Laboratory, Diabetes and Nutritional Sciences Division , Rayne Institute, St Thomas Hospital, King's College London , London , UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Ciclitira
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D002446:Celiac Disease / Q000209:etiology* / Q000276:immunology; D002460:Cell Line; D005260:Female; D005983:Glutens / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D007422:Intestines / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009924:Organ Culture Techniques; D010455:Peptides / Q000276:immunology / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D010455:Peptides; D005983:Glutens; C037302:glutenin
keywords: Coeliac disease; T-cell proliferation assay; glutenins; organ culture