Sturgess, Richard Patrick;
(1996)
Investigation of the cellular immunopathogenesis and cereal toxicity of coeliac disease.
Doctoral thesis (M.D), UCL (University College London).
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Abstract
Coeliac disease is characterised by small intestinal enteropathy resulting from the ingestion of certain dietary cereals by genetically predisposed individuals. Immunological factors are thought to be involved in the pathogenesis of the intestinal lesion but the precise mechanisms remain unknown. The exact nature of the active moiety within coeliac toxic cereals has not been defined. The aims of this thesis were to investigate (i) small intestinal cellular adhesion mechanisms involved in coeliac disease (ii) γδ T cell populations within the intestinal mucosa of patients with coeliac disease and dermatitis herpetiformis and (iii) cereal toxicity in coeliac disease by in vivo challenge with synthetic giadin oligopeptides. Immunohistochemistry and organ culture was used to study the expression of intercellular adhesion molecule-1 (ICAM-1) within the small intestinal mucosa. Differential upregulation of ICAM-1 was demonstrated in the intestine of coeliac patients, with marked increases within the lamina propria but not the epithelium. Increased expression occurred rapidly, following gluten challenge in treated coeliac patients. The cytokines interferon-y and tumour necrosis factor-a induced increased expression of ICAM-1 within the lamina propria of cultured jejunal biopsies from normal patients. These studies suggest that the lamina propria is a major site of immune activation in coeliac disease. T lymphocytes expressing the γδ form of the T cell receptor were found to be increased in the intestinal mucosa in both coeliac disease and dermatitis herpetiformis. The increased numbers of γδ+T cells correlated with morphometric indices of enteropathy. Local gluten challenge in the rectal mucosa of coeliac patients showed that the early lymphocyte response did not involve γδ+ T cells. Three peptides corresponding to amino acids 3-21, 31-49 and 202-220 of A-gliadin were synthesised. Four treated coeliac patients underwent acute in vivo challenges with each of the oligopeptides. Coeliac toxicity was confined, with the exception of one patient, to the oligopeptide corresponding to amino-acids 31-49 of A-gliadin.
Type: | Thesis (Doctoral) |
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Qualification: | M.D |
Title: | Investigation of the cellular immunopathogenesis and cereal toxicity of coeliac disease |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Additional information: | Thesis digitised by ProQuest. |
Keywords: | Health and environmental sciences; Celiac disease |
URI: | https://discovery.ucl.ac.uk/id/eprint/10100657 |
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