The immunology of coeliac disease

Conclusions Whether or not the immune system initiates CD, it can be seen to play a role in the natural history of the disease. Genetic susceptibility to CD has been shown to be linked to the HLA, DQw2 and it appears that other genes within the MHC further contribute to disease susceptibility. The search for other immune response genes that may be linked to CD has lead to investigation both within the MHC and elsewhere in the genome. However, environmental factors undoubtedly contribute to the pathogenesis of the disease.The initiating event leading to CD may be exposure to gluten or possibly infection with a virus. Although it has been suggested that the lesions of CD may be a direct consequence of chemical damage caused by gluten, the weight of evidence suggests that damage occurs either as a result, or as a consequence, of the immune response to gluten. Epithelial damage may result from the immune response directed against antigens processed and presented by epithelial cells. Alternatively epithelial damage may be a consequence of the local immune response to absorbed wheat antigens, or possibly other luminal antigens leaking into the mucosa due to increased intestinal permeability.Whether this immune response develops as the result of a cross-reactivity between a viral peptide and a gluten-derived peptide remains to be seen. Histological, immunocytochemical and serological studies clearly demonstrate the involvement of the immune system in established CD. A deeper understanding of the genetic susceptibility to CD, the identity of the immunogenic gluten peptides and the interaction between antigen HLA and lymphocytes will not only help us to understand CD but also provide an insight into many other immune-mediated diseases.