WHEAT PEPTIDE CHALLENGE IN CELIAC-DISEASE

The exact nature of the cereal moiety that exacerbates coeliac disease is unknown. In-vitro studies have implicated both the N-terminal and far C-terminal domains of one of the wheat prolamins, A-gliadin. Pepti des within these regions may act as epitopes that trigger immune event s leading to enteropathy. We synthesised three peptides corresponding to aminoacids 3-21, 31-49, and 202-220 of A-gliadin. Four patients wit h coeliac disease were challenged by intraduodenal infusion of 1 g of gliadin or 200 mg of the synthetic peptides. Jejunal biopsies were tak en before and at hourly intervals for 6 h after the infusion. Morphome tric variables were measured and intraepithelial lymphocytes counted. Significant histological changes occurred in the small intestinal muco sa after challenge with a synthetic peptide corresponding to amino aci ds 31-49 of A-gliadin. The N-terminal peptide, residues 3-21 of A-glia din, did not cause histological changes in any of the patients. In one of the four patients, minor histological changes following challenge with the peptide corresponding to residues 202-220 of A-gliadin were s een. Our results suggest that the oligopeptide corresponding to aminoa cids 31-49 of A-gliadin is toxic in vivo, but there is no evidence of toxicity of the far N-terminal peptide, residues 3-21. The C-terminal peptide 202-220 may contain an epitope to which patients with coeliac disease display variable sensitivity. Since the oligopeptide correspon ding to aminoacids 31-49 of A-gliadin is recognised by HLA DQ2-restric ted T cells, the observed effects may be due to immune activation with in the intestinal mucosa.