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| Article Authors: | R Sturgess; P Day; H J Ellis; K E Lundin; H A Gjertsen; M Kontakou; P J Ciclitira |
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| Article Title: | Wheat peptide challenge in coeliac disease. |
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| Reference ID: | 1005306 |
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| Abstract: | 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. |
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| Affiliations: | Rayne Institute Division of Pharmacology, St Thomas' Hospital, London, UK. |
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| Date: | 1994 |
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| Reference Type: | Literature |
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| PubMed ID: | 7907731 |
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| Journal: | Lancet |
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| Journal Volume: | 343 |
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| Article Pages: | 758-61 |
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| Journal ISSN: | 0140-6736 |
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| Article Chemical List: | Allergens;Antigens, CD3;Peptides;Gliadin |
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| Article MeSH List: | Adult; Aged; Allergens; Amino Acid Sequence; Antigens, CD3(immunology ); Celiac Disease(immunology ); Female; Gliadin(chemical synthesis; immunology ); Humans; Intestinal Mucosa(immunology; pathology ); Intestine, Small(immunology; pathology ); Leukocyte Count; Male; Middle Aged; Molecular Sequence Data; Peptides(chemical synthesis; immunology ); Triticum |
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| Curation Last Updated: | 2013-04-25 20:04:42 |
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