Celiac disease, also known as gluten-sensitive enteropathy or nontropical sprue, is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten. The primary target of the disease is the small intestine; celiac disease can affect multiple systems, however.
|CELIAC DISEASE AND MALABSORPTION|
It is primarily seen in individuals of European descent but is increasingly recognized on almost every continent. The overall prevalence in the general population of the United States and Europe is nearly 1%; only 10% to 15% of patients have been diagnosed and treated, however. The prevalence appears to increase with age. Celiac disease develops in genetically predisposed individuals as a result of the influence of environmental factors. First-degree relatives of patients with celiac disease have a 10% to 15% risk of developing the disease. The HLA class II genes HLA-DQ2 and HLA-DQ8, which are normally expressed on the surface of antigen cells in the gut, are the most important genetic susceptibility factors in celiac disease. HLA-DQ2 is found in 90% to 95% of patients with celiac disease, with HLA-DQ8 found in most of the remaining patients. These molecules are necessary variables predisposing a patient to the disease, which means that celiac disease is unlikely if neither molecule is present. The molecules are not, however, sufficient to cause celiac disease; they occur in 30% to 40% of the general population. Gluten is a storage protein of wheat. The alcohol-soluble fraction of gluten, gliadin, is toxic in celiac disease, along with similar proteins in barley (hordeins) and rye (secalins). These proteins are rich in glutamine and proline residues that even the healthy human intestine cannot fully digest. As a result, intact gliadin peptides are left in the lumen, but few cross the intestinal barrier. In individuals with celiac disease, these fragments come into contact with tissue transglutaminase, a ubiquitous intracellular enzyme that is released by inflammatory and endothelial cells and fibroblasts in response to mechanical irritation or inflammation. Upon contact, tissue transglutaminase cross-links with these glutamine-rich proteins and deamidates them. This process modifies glutamine residues into glutamic acid residues, which are ideally suited to interact with the HLA-DQ2 or HLA-DQ8 molecules. Once bound to HLA-DQ2 or HLA-DQ8, gliadin peptides are presented to the CD4+ T cells, triggering the inflammatory reaction. The end result is an inflammatory state of the small intestine, causing a derangement in the architecture of the mucosa, with flattening of the villi, and infiltration of lymphocytes into the epithelium.