title: Pathophysiology of celiac disease.
abstract: Celiac disease (CD) is strongly associated with HLA-DQ2 and HLA-DQ8, HLA-class II molecules that present antigen-derived peptides to CD4 T cells. Indeed, proinflammatory CD4 T cells specific for gluten-derived peptides bound to HLA-DQ2 or HLA-DQ8 are present in the lamina propria of patients, and not found in nonceliac controls. While gluten peptides bind poorly to HLA-DQ2/8, modification by tissue tranglutaminase converts the neutral amino acid glutamine into glutamic acid, introducing a negative charge that allows high affinity binding. Thus, the association between CD and HLA-DQ2/8 is well understood. What is less clear is why only a small minority of HLA-DQ2/8 positive individuals develops CD, why disease can develop at any stage in life and present with highly variable symptoms. I discuss this in the framework of the multiple hit model: next to genetic predisposition, multiple other factors-some extrinsic, some intrinsic-can favour or protect from disease development.
authors: Frits
authors: F
authors: Koning
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002446:Celiac Disease / Q000276:immunology*; D004198:Disease Susceptibility; D018698:Glutamic Acid / Q000378:metabolism; D005983:Glutens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D018698:Glutamic Acid; D005983:Glutens; D011503:Transglutaminases