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• W2078462317 abstract "In the small intestine of celiac disease patients, dietary wheat gluten and similar proteins in barley and rye trigger an inflammatory response. While strict adherence to a gluten-free diet induces full recovery in most patients, a small percentage of patients fail to recover. In a subset of these refractory celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte population develops into overt lymphoma. Celiac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease development. This association can be explained by the fact that gluten peptides can be presented in HLA-DQ2 and HLA-DQ8 molecules on antigen presenting cells. Gluten-specific CD4+ T cells in the lamina propria respond to these peptides, and this likely enhances cytotoxicity of intraepithelial lymphocytes against the intestinal epithelium. We propose a threshold model for the development of celiac disease, in which the efficiency of gluten presentation to CD4+ T cells determines the likelihood of developing celiac disease and its complications. Key factors that influence the efficiency of gluten presentation include: (1) the level of gluten intake, (2) the enzyme tissue transglutaminase 2 which modifies gluten into high affinity binding peptides for HLA-DQ2 and HLA-DQ8, (3) the HLA-DQ type, as HLA-DQ2 binds a wider range of gluten peptides than HLA-DQ8, (4) the gene dose of HLA-DQ2 and HLA-DQ8, and finally,(5) additional genetic polymorphisms that may influence T cell reactivity. This threshold model might also help to understand the development of refractory celiac disease and lymphoma." @default.
• W2078462317 created "2016-06-24" @default.
• W2078462317 creator A5062100129 @default.
• W2078462317 creator A5064137254 @default.
• W2078462317 creator A5064835819 @default.
• W2078462317 date "2010-07-27" @default.
• W2078462317 modified "2023-09-30" @default.
• W2078462317 title "Celiac disease: how complicated can it get?" @default.
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• W2078462317 doi "https://doi.org/10.1007/s00251-010-0465-9" @default.
• W2078462317 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2944025" @default.
• W2078462317 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20661732" @default.
• W2078462317 hasPublicationYear "2010" @default.
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