Celiac disease (also known as coeliac disease, celiac sprue, nontropical sprue, and gluten-sensitive enteropathy) is an autoimmune disorder in which the ingestion of gluten, found in wheat-, rye-, and barley-containing products, leads to progressive damage of the mucosal lining of the small intestine. It is typically diagnosed based on the presence of specific antibodies (antigliadin, antiendomysial, and antitissue transglutaminase) in the blood of affected individuals, characteristic histological findings on small bowel biopsy, and a positive response to a gluten-free diet. The clinical manifestations associated with celiac disease are extremely variable. While the classic triad of features (malabsorption, chronic diarrhea, and failure to thrive) is common, many individuals with celiac disease present with more atypical symptoms, many of which are unrelated to the digestive system. Gastrointestinal symptoms may include abdominal pain, constipation, weight loss, lactose intolerance, irritable bowel syndrome, and abdominal distention. Nongastrointestinal symptoms may include iron-deficient anemia, dermatitis herpetiformis (a blistering skin rash), chronic fatigue, joint pain, migraines, infertility, short stature, delayed puberty, psychiatric disorders, and defects of the dental enamel. In addition, patients with celiac disease are at an increased risk for other autoimmune disorders, such as type 1 diabetes mellitus or thyroiditis, and may have an increased risk for certain malignancies, if untreated. Treatment of celiac disease with a gluten-free diet can eliminate the symptoms of the disease and may result in a normalization of small bowel histology. The prevalence of celiac disease varies by population background, but it is estimated that approximately 1 in 100 Americans has the disease, many of whom remain undiagnosed. Celiac disease is a multifactorial disorder that results from the interactions of 2 human leukocyte antigen (HLA) genes with non-HLA genes and various environmental factors (including gluten exposure). The HLA-DQA1 and HLA-DQB1 genes, both of which are located on chromosome 6 at band p21.3, encode the alpha and beta chains of HLA heterodimers. Approximately 90% to 95% of individuals with celiac disease carry either the DQA1*0501 allele or the DQA*0505 allele, along with either the DQB1*0201 allele or the DQB1*0202 allele, and express the DQ2 HLA molecule. Most of the remaining 5% to 10% of patients carry DQA1*03 and DQB1*0302 alleles and express the DQ8 HLA molecule. In individuals with celiac disease, the DQ2 and DQ8 heterodimers bind gluten peptides and present them to T cells, triggering an immune response and subsequent tissue damage in the small intestine. However, DQ2 and DQ8 heterodimers are also found in approximately 25% to 40% of healthy individuals, suggesting that specific HLA genotypes are necessary, but not sufficient, for the development of celiac disease.