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Celiac disease: how complicated can it get?
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 r...
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944025/ https://www.ncbi.nlm.nih.gov/pubmed/20661732 http://dx.doi.org/10.1007/s00251-010-0465-9 |
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author | Tjon, Jennifer May-Ling van Bergen, Jeroen Koning, Frits |
author_facet | Tjon, Jennifer May-Ling van Bergen, Jeroen Koning, Frits |
author_sort | Tjon, Jennifer May-Ling |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2944025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-29440252010-10-12 Celiac disease: how complicated can it get? Tjon, Jennifer May-Ling van Bergen, Jeroen Koning, Frits Immunogenetics Review 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. Springer-Verlag 2010-07-27 2010 /pmc/articles/PMC2944025/ /pubmed/20661732 http://dx.doi.org/10.1007/s00251-010-0465-9 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Review Tjon, Jennifer May-Ling van Bergen, Jeroen Koning, Frits Celiac disease: how complicated can it get? |
title | Celiac disease: how complicated can it get? |
title_full | Celiac disease: how complicated can it get? |
title_fullStr | Celiac disease: how complicated can it get? |
title_full_unstemmed | Celiac disease: how complicated can it get? |
title_short | Celiac disease: how complicated can it get? |
title_sort | celiac disease: how complicated can it get? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944025/ https://www.ncbi.nlm.nih.gov/pubmed/20661732 http://dx.doi.org/10.1007/s00251-010-0465-9 |
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