Genetic (Human Leukocyte Antigen) Testing for Celiac Disease
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 the 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.
Genetic testing for HLA-DQ2 and/or HLA-DQ8 alleles to rule out celiac disease is considered medically necessary if the medical appropriateness criteria are met (See Medical Appropriateness below).
Genetic testing for HLA-DQ2 and/or HLA-DQ8 alleles as a screening tool, to determine risk for Celiac disease in asymptomatic individuals, or rule out any other conditions/diseases is considered investigational.
Genetic testing for Human Leukocyte Antigen (HLA-DQ2 and/or HLA-DQ8) alleles to rule out Celiac disease is considered medically appropriate if ANY ONE of the following are met:
Discordant findings in ALL of the following:
Serologic ( e.g. tTG-IgA, EMA-IgA, tTG IgG, EMA IgG, AGA)
Histologic (biopsy) results
Persistent symptoms suggestive of Celiac disease (e.g. diarrhea, abdominal pain, bloating) despite negative serologic and histologic findings
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Several studies have reported that the sensitivity of a negative predictive value for human leukocyte antigen (HLA) testing for celiac disease approached 100%, meaning that this test is highly accurate for ruling out Celiac disease (CD). Determining genetic susceptibility can avoid unnecessary repeat testing, and initiation of a gluten-free diet, especially in individuals in high-risk groups (e.g. those with other autoimmune disorders, those with a first degree relative with CD and type 1 diabetes mellitus).
Aggarwal, S., Lebwohl, B., & Green, P. H. R. (2012). Screening for celiac disease in average-risk and high-risk populations. Therapeutic Advances in Gastroenterology, 5 (1), 37-47. (Level 1 evidence - Independent)
American College of Gastroenterology. (May, 2013). ACG clinical guidelines: diagnosis and management of celiac disease. Retrieved July 7, 2015 from the National Guideline Clearing house (NGC: 45327).
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2015) Human leukocyte antigen testing for celiac disease (2.04.95) Retrieved March 17, 2017 from BlueWeb. (11 articles and/or guidelines reviewed)
Cahaba Government Benefits Administrator, LLC (2015, October) Local Coverage Determination (LCD):Pathology and Laboratory: Molecular Pathology Procedures for Human Leukocyte Antigen (HLA) Typing (L34943).Retrieved March 24, 2017 from: https://www.cms.gov.
DePalma, G., Capilla, A., Nova, E., Castillejo, G., Varea, V., Pozo, T., et al. (2012). Influence of milk-feeding type and genetic risk of developing coeliac disease on intestinal microbiota of infants: The PROFICEL study. PloS ONE, 7 (2), e30791. (Level 2 Evidence - Independent study)
Harris, L., Park, J., Voltaggio, L., & Lam-Himlin, D. (2012). Celiac disease; clinical, endoscopic, and histopathologic review. Gastrointestinal Endoscopy. 76 (3), 625-640. (Level 5 evidence)
Hojsak, I., Mozar-Glassberg, Y., Gilboa, N. S., Weinberger, R., Hartman, C., & Shamir, R. (2012). Celiac disease screening assays for children younger than 3 years of age: The performance of three serological tests. Digestive Diseases and Sciences, 57 (1), 127-132. (Level 3 evidence)
Konopka, E., Grzywnowicz, M., Oralewska, B., Cielecka-Kuszyk, J., Trojanowska, I., & Cukrowska, B. (2016). Clinical utility of quantitative multi-antibody Polycheck immunoassays in the diagnosis of coeliac disease. World Journal of Gastrointestinal Pharmacology and Therapeutics, 7 (2), 254-260. (Level 3 evidence)
Mills, J. R., & Murray, J. A. (2016). Contemporary celiac disease diagnosis: is a biopsy avoidable? Current Opinion in Gastroenterology, 32 (2), 80-85. Abstract retrieved June 3, 2016 from PubMed database.
National Institute for Health and Care Excellence. NICE Guidance. (2015, September). Coeliac disease: recognition, assessment and management. Retrieved June 3, 2016 from https://www.nice.org.uk.
North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) (2004) Guideline for the Diagnosis and Treatment of Celiac Disease in Children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Retrieved March 17, 2017 from: http://www.naspghan.org.
Oyaert, M., Vermeersch, P., De Hertogh, G., Hiele, M., Vandeputte, N., Hoffman, I., et al. (2015). Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease. Clinical Chemistry and Laboratory Medicine. Abstract retrieved July 7, 2015 from PubMed database.
U. S. Food and Drug Administration. (2008, February). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K073145. Retrieved February 14, 2012 from http://www.accessdata.fda.gov.
U. S. Food and Drug Administration. (2010, August). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K093459. Retrieved February 14, 2012 from http://www.accessdata.fda.gov.
U. S. Food and Drug Administration. (2011, June). Center for Devices and Radiological Health. 510(k) Premarket Notification Database. K102490. Retrieved February 14, 2012 from http://www.accessdata.fda.gov.
Zhao,K., Miao, K., Waugh, K., Iman, T., Dong, F., Liu, E., et. al. (2016, September) Higher sensitivity and earlier identification of celiac disease autoimmunity by a nonradioactive assay for transglutaminase autoantibodies. Journal of Immunology Research. Vol. 2016, Article ID 2904563. (Level 3 evidence)
ORIGINAL EFFECTIVE DATE: 7/11/2011
MOST RECENT REVIEW DATE: 8/12/2017
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