Article ; Online: Celiac disease: how complicated can it get?
2010 Volume 62, Issue 10, Page(s) 641–651
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 ... ...
| 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. |
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| MeSH term(s) | Adult ; Antigen Presentation ; CD4-Positive T-Lymphocytes/immunology ; Celiac Disease/epidemiology ; Celiac Disease/genetics ; Celiac Disease/immunology ; Child ; Child, Preschool ; Cytotoxicity, Immunologic ; Disease Progression ; GTP-Binding Proteins ; Gene Dosage ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Glutens/immunology ; HLA-DQ Antigens/genetics ; HLA-DQ Antigens/immunology ; Humans ; Immunity, Mucosal ; Intestine, Small/immunology ; Intestine, Small/pathology ; Lymphoma, B-Cell, Marginal Zone/etiology ; Models, Immunological ; Prevalence ; Transglutaminases/physiology |
| Chemical Substances | HLA-DQ Antigens ; HLA-DQ2 antigen ; HLA-DQ8 antigen ; Glutens (8002-80-0) ; transglutaminase 2 (EC 2.3.2.-) ; Transglutaminases (EC 2.3.2.13) ; GTP-Binding Proteins (EC 3.6.1.-) |
| Language | English |
| Publishing date | 2010-07-27 |
| Publishing country | United States |
| Document type | Journal Article ; Review |
| ZDB-ID | 186560-2 |
| ISSN | 1432-1211 ; 0093-7711 |
| ISSN (online) | 1432-1211 |
| ISSN | 0093-7711 |
| DOI | 10.1007/s00251-010-0465-9 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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