Celiac disease is a chronic immune-mediated inflammatory disorder with multi-systemic manifestations, both gastrointestinal and nongastrointestinal. In genetically susceptible individuals, ingestion of gluten can cause inflammation and damage to the small intestine mucosa. Celiac disease has an incidence of 1:100 in the United States.

In order for celiac disease to develop, human leukocyte antigen (HLA) molecule DQ2, half of the DQ2 molecule, or DQ8 must be present. These molecules confer susceptibility to celiac disease by binding to gluten and interacting with intestinal T cells, leading to a pathologic immune response involving autoimmunity. The familial nature of susceptibility to celiac disease is shown by an 11-18% prevalence of this disorder in siblings of individuals with celiac disease and a 70% concordance rate between identical twins.

Among celiac disease patients, >90% carry DQ2, 5-10% carry DQ8, and the remaining carry half DQ2.

- The presence of DQ2, half DQ2, or DQ8 alone is not sufficient for a diagnosis of celiac disease.

- Most individuals with a positive genetic result do not develop celiac disease.

- The risk for developing celiac disease in individuals with a positive genetic result approaches 40% if there is a known first degree relative with celiac disease.

Clinical symptoms, positive test results for endomysial, tissue transglutaminase or deamidated gliadin peptide antibodies, or abnormal small bowel biopsy results all support a diagnosis of celiac disease.

The overall risk for an individual to develop celiac disease is influenced not just by genetic risk from the HLA-DQA/DQB genotype, but by presence of symptoms of celiac disease, positive results for celiac antibody tests or intestinal biopsy, and having relatives with celiac disease.

Celiac disease risk is also higher in individuals with IgA deficiency, Down syndrome, Turner syndrome, and the autoimmune disorders Type I diabetes mellitus, Sjogren syndrome, and thyroiditis. There are also additional genetic influences on the development of celiac disease in individuals predisposed to the disorder.

References:

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- Sollid LM and Lie BA. (2005). Celiac Disease Genetics: Current Concepts and Practical Applications. Clin Gastroenterol and Hepat 3:843-851.

- Snyder CL, Young DO, Green PHR, et al. Celiac Disease. In: Pagon RA, Bird TC, Dolan CR, Stephens K, editors. GeneReviews (Internet), University of Washington, Seattle, July 3, 2008:1-27. http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=genepart=celiac PMID 20301720 (PubMed)

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