Wheat peptide challenge in coeliac 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. Peptides within these regions may act as epitopes that trigger immune events leading to enteropathy. We synthesized three peptides corresponding to amino-acids 3-21, 31-49, and 202-220 of A-gliadin. Four patients with coeliac disease were challenged by intraduodenal infusion of 1 g of gliadin or 200 mg of the synthetic peptides. Jejunal biopsies were taken before and at hourly intervals for 6 h after the infusion. Morphometric variables were measured and intraepithelial lymphocytes counted. Significant histological changes occurred in the small intestinal mucosa after challenge with a synthetic peptide corresponding to amino acids 31-49 of A-gliadin. The N-terminal peptide, residues 3-21 of A-gliadin, 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 seen. Our results suggest that the oligopeptide corresponding to aminoacids 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 corresponding to amino-acids 31-49 of A-gliadin is recognised by HLA DQ2-restricted T cells, the observed effects may be due to immune activation within the intestinal mucosa.
Sturgess
R
R
Rayne Institute Division of Pharmacology, St Thomas' Hospital, London, UK.
Day
P
P
Ellis
H J
HJ
Lundin
K E
KE
Gjertsen
H A
HA
Kontakou
M
M
Ciclitira
P J
PJ
D000328:Adult; D000368:Aged; D000485:Allergens; D000595:Amino Acid Sequence; D017252:CD3 Complex / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology*; D005260:Female; D005903:Gliadin / Q000138:chemical synthesis / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D014908:Triticum
D000485:Allergens; D017252:CD3 Complex; D010455:Peptides; D005903:Gliadin