BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic (Human Leukocyte Antigen) Testing for Celiac Disease

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018


Celiac disease (CD) is an autoimmune disorder where the ingestion of gluten leads to damage in the small intestine. Either one or both of the human leukocyte antigen (HLA) DQ2 or DQ8 genes are carried by individuals with celiac disease; however, up to 30% of the general population also carries one or both of these genes. A negative gene test would exclude having or ever having the disease, but a positive result would not necessarily mean the individual has celiac disease. Celiac disease (CD), which is also referred to as celiac sprue or gluten-sensitive enteropathy, may be defined as small intestinal inflammation resulting from an immunologic intolerance to gluten (i.e., the proteins derived from wheat, barley, and rye).

Celiac disease may develop at any time from infancy to adulthood. In children, the disease typically presents between 6 and 24 months, and is characterized by abnormal stools, poor appetite, and irritability. In adults, diarrhea, bloating, abdominal pain are usually the presenting symptoms. Definitive diagnosis is based on small intestinal biopsies showing a flattened intestinal mucosa in association with an inflammatory infiltrate. Blood tests for IgA antibody deficiencies such as Tissue Transglutaminase Antibodies (tTG-IgA) will be positive in about 98% of individuals who are on a gluten-containing diet. Other antibody tests, such as IgA endomysial antibody (EMA) and deaminated gliadin peptide (DGP IgA and IgG) are available to double-check for potential false positives or false negatives.





American College of Gastroenterology. (May, 2013). ACG clinical guidelines: diagnosis and management of celiac disease. Retrieved May 14, 2018 from

BlueCross BlueShield Association. Evidence Positioning System. (12:2019). Human leukocyte antigen testing for celiac disease (2.04.95). Retrieved March 26, 2020 from (13 articles and/or guidelines reviewed)

Children’s Digestive Health and Nutrition Foundation. North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN). (2016). Diagnosis and treatment of celiac disease in children, clinical practice guideline summary. Retrieved March 17, 2017 from

National Institute for Health and Care Excellence. (2015, September). Coeliac disease: recognition, assessment and management. Retrieved June 3, 2016 from  

Werkstetter, K.J., Korponay-Szabó, I.R., Popp, A., Villanacci, V., Salemme, M., Heilig, G., et al. (2017). Accuracy in diagnosis of celiac disease without biopsies in clinical practice. Gastroenterology, 153 (4), 924-935. Abstract retrieved March 20, 2019 from PubMed database.




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