Coeliac disease: in vivo toxicity of the putative immunodominant epitope

• Published in: Gut Vol. 52; no. 12; pp. 1698 - 1702
• Main Authors: Fraser, J S, Engel, W, Ellis, H J, Moodie, S J, Pollock, E L, Wieser, H, Ciclitira, P J
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01-12-2003; BMJ; BMJ Publishing Group Ltd; BMJ Publishing Group LTD; Copyright 2003 by Gut
• Subjects: Aged; Amino acids; Antigenic determinants; Biological and medical sciences; Biopsy, Needle; Blood cells; Care and treatment; Causes of; Celiac disease; Celiac Disease - immunology; Celiac Disease - pathology; Chromatography; Cloning; coeliac disease; Colorectal diseases; Cytokines; ECH; enterocyte surface cell height; Experiments; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal diseases; Genetic aspects; Gliadin - immunology; Gliadin - toxicity; Gluten; Health aspects; high pressure liquid chromatography; HPLC; Humans; IEL; IFN-γ; Immunohistochemistry; Interferon gamma; interferon γ; Intestine, Small - immunology; Intestine, Small - pathology; intraepithelial lymphocytes; Lymphocytes; Male; Medical research; Medical sciences; mucosal immunity; Mucosal Immunology; Other diseases. Semiology; Patients; PCR; peptic-tryptic digest of gliadin; peptide challenge; Peptide Fragments - immunology; Peptide Fragments - toxicity; Peptides; Physiological aspects; polymerase chain reaction; PTG; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; TEAF; tissue transglutaminase; toxic epitope; Toxicity; Toxins; triethylammonium formate; tTG; VH:CD; villus height to crypt depth ratio; United States; Human; Immunopathology; Antigenic determinant; Monocyte; Biosynthesis; Coeliac disease; Experimental study; Biological activity; Intestinal malabsorption; Gliadin; Digestive diseases; Intestinal disease; Gamma interferon
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.52.12.1698

Background: Peptides from α-gliadins have been used to characterise the immunodominant coeliac toxic epitope. A peptide corresponding to amino acid residues 57–73 of A-gliadin causes peripheral blood mononuclear cells from coeliac patients to secrete interferon γ (IFN-γ); gluten specific small intestinal T cell clones proliferate in response to peptides corresponding to residues 57–68 and 62–75 of α-gliadins. We wished to investigate whether a peptide corresponding to residues 56–75 of α-gliadins exacerbates coeliac disease in vivo. Methods: Four adults with coeliac disease, all of whom were on a gluten free diet, underwent three challenges. Peptic-tryptic gliadin (PTG 1 g) served as a positive control. The test peptide and a negative control peptide were studied on separate occasions. The peptides were instilled into the duodenum and biopsies were taken before the infusion, and two, four, and six hours after commencing the infusions, using a Quinton hydraulic multiple biopsy capsule. Biopsy specimens were assessed blindly for villus height to crypt depth ratio (VH:CD), enterocyte cell height (ECH), and intraepithelial lymphocyte (IEL) count. We used the Mann-Whitney U test, with 95% confidence intervals, for statistical analysis. Results: VH:CD and ECH fell, and IEL increased significantly 4–6 hours after commencing infusions with both PTG and the test peptide in all subjects. The negative control peptide caused no significant changes to villus morphology, enterocyte height, or IEL count in any patient. Conclusion: We have confirmed that the putative immunodominant epitope, a peptide corresponding to residues 56–75 of α-gliadins, exacerbates coeliac disease in vivo.