For Physicians Overview
Celiac disease is an acquired chronic autoimmune disorder that develops in genetically susceptible individuals of HLA genotype DQ2 or DQ8 after exposure to an environmental factor, gluten [(Kim, Quarsten et al. 2004; Rostom, Dube et al. 2005; Van Heel and West 2006; Green and Cellier 2007) and references therein]. Gluten refers to a family of proteins in wheat, barley and rye that are especially abundant in glutamine (~35%) and proline (~15%) residues (Stern, Ciclitira et al. 2001; Weiser 1995), rendering them unusually resistant to digestion by gastric, pancreatic, and intestinal brush border membrane proteases, as these enzymes have poor specificity for peptide bonds adjacent to proline and glutamine (Hausch, Shan et al. 2002; Shan, Molberg et al. 2002; Marti, Molberg et al. 2005; Gass, Vora et al. 2006). Gliadin is the alcohol-soluble fraction of gluten that contains the bulk of the immunogenic peptides. As a consequence of the incomplete gastrointestinal proteolysis of gluten, long oligopeptides accumulate in the small intestine of mammals following ingestion of gluten. These peptides (including a peptide made up of 33 amino acids termed the “33mer”) are recognized by specialized antigen presenting cells (APCs) in celiac disease patients, which then trigger a specific T lymphocyte-driven immune response in celiac disease patients (Shan, Molberg et al. 2002; Shan, Qiao et al. 2005; Jabri and Sollid 2006; Kagnoff 2007). In the small bowel of celiac disease patients, persistent inflammation results in atrophy of cells in the villus tips and hypertrophy of cells in the villus crypts (Shiner 1973; Marsh and Crowe 1995; Rostom, Murray et al. 2006; Kagnoff 2007).
The prevalence of celiac disease in the United States has been estimated to be approximately 1%-2% of the population (Shan, Qiao et al. 2005; Van Heel and West 2006; Green 2007). Once considered a rare malabsorptive syndrome of childhood, celiac disease is now recognized as a common condition that may be diagnosed at any age and affects many organ systems. It has a wide range of clinical manifestations including chronic gastrointestinal symptoms, malabsorption, weight loss, anemia, dermatitis herpetiformis, elevated liver enzyme levels, osteoporosis, etc. (Rostom, Murray et al. 2006; Van Heel and West 2006; Green and Cellier 2007). For all patients, celiac disease is a lifelong disease, and unless complete gluten exclusion is strictly followed, patients have an enhanced risk for the development of further complications, such as further bone loss, infertility, cancer and increased mortality (Peters, Askling et al. 2003).