RT Journal Article
SR Electronic
T1 Coeliac disease: in vivo toxicity of the putative immunodominant epitope
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1698
OP 1702
DO 10.1136/gut.52.12.1698
VO 52
IS 12
A1 J S Fraser
A1 W Engel
A1 H J Ellis
A1 S J Moodie
A1 E L Pollock
A1 H Wieser
A1 P J Ciclitira
YR 2003
UL http://gut.bmj.com/content/52/12/1698.abstract
AB 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.