Celiac disease. A gastrointestinal disease with environmental, genetic, and immunologic components.
In summary, research in immunogenetics, protein chemistry, and molecular biology is leading to a greater understanding of the contribution of genetic, environmental, and immunologic factors to the etiopathogenesis of celiac disease. Taken together, the findings discussed in this article suggest that understanding of the contribution of a major genetic factor to celiac disease susceptibility is closer at hand. Thus, the pathogenesis of celiac disease appears to involve an interaction between the gene products of the HLA class II D region on chromosome 6 and the gliadin proteins, possibly because of their homology with an intestinal viral protein. A logical extension of these findings would predict that T cells, particularly CD4 T cells, play a key role in the pathogenesis of celiac disease by virtue of their recognition of a gliadin or viral peptide in conjunction with the HLA class II D-region gene products. Nonetheless, the precise mechanisms by which the HLA class II genes and their products contribute to celiac disease is not known. Further, the precise peptide sequence in gliadin that interacts with the relevant HLA class II D-region molecule is not known. Finally, the role of CD4 T cells in the pathogenesis of celiac disease, either directly or indirectly by their ability to regulate other T-cell subsets and antibody-producing B cells, remains to be defined. The lessons learned and to be learned from celiac disease will substantially increase our understanding of the mechanisms that are important in this disease as well as in other intestinal and HLA-associated autoimmune diseases.
Kagnoff
M F
MF
Department of Medicine, University of California, San Diego, La Jolla.
D000917:Antibody Formation; D002446:Celiac Disease / Q000150:complications / Q000175:diagnosis / Q000178:diet therapy / Q000235:genetics / Q000276:immunology; D004781:Environmental Exposure; D005802:Genes, MHC Class II / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular