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Serologic Diagnosis of Celiac Disease

Policy Number: MP-161

Latest Review Date: May 2022

Category: Laboratory


Serologic measurement of antigliadin (AGA), antiendomysial or tissue transglutaminase antibodies may be considered medically necessary when:

  • Performed to evaluate patients with signs or symptoms suggestive of celiac disease; OR
  • Performed to monitor patient’s adherence and response to a gluten-free diet

Serologic measurement of deamidated gliadin peptide antibodies (DGP) is considered investigational in patients with signs or symptoms suggestive of celiac disease.

Screening of asymptomatic, at risk patient groups, for celiac disease using one or more serologic IgA or IgG measures is considered investigational.

Population screening for celiac disease using one or more serologic IgA or IgG measures is considered investigational.


Celiac disease is an immune disorder in which individuals are unable to tolerate gluten, a protein found in wheat, rye, and barley. Diagnosis is made based on the biopsy and histopathologic examination of the small intestine. Blood tests may be used to select individuals for biopsy and to aid in diagnosis. Celiac disease is characterized by an abnormal proximal small intestinal mucosa, and it is associated with a permanent intolerance to gluten. Both the symptoms and abnormal small intestinal mucosal morphology resolve with removal of gluten from the diet.

Because the symptoms of celiac disease are nonspecific they are often overlooked. In addition, the disease may develop at any time in life, from infancy to very old age. In adults, diarrhea is the main presenting symptom, but presenting symptoms may be entirely nonspecific, such as anemia or infertility. Celiac disease is associated with a number of other conditions, including Type 1 diabetes mellitus, rheumatoid arthritis, and primary biliary cirrhosis.


The most recent literature update was performed through May 11, 2022.

Summary of Evidence

Use of serologic tests for the diagnosis of celiac disease has the potential to reduce the need for intestinal biopsies and thus improve the efficiency of diagnosis. Evidence from systematic reviews and head-to-head comparative studies using biopsy as the gold standard is adequate to conclude that tissue transglutaminase and antiendomysial antibody tests are sufficiently accurate for identifying celiac disease in patients with signs or symptoms of the disease. These tests are appropriate for use as the diagnostic test for celiac disease and will reduce the need for intestinal biopsy without substantially lowering the accuracy of diagnosis. It should be noted, however, that the most important initial step in diagnosis is recognition of the many clinical features that can be associated with the disease.

In children younger than two years-old, the pattern of serologies appears to be different than in older individuals. Evidence found that in children younger than 18 months, serologic measurement of antigliadin antibodies (AGA) is the most sensitive testing.

The evidence for serologic measurement of deamidated gliadin peptide antibodies (DGP) for celiac disease remains controversial and unproven as superior to the gold standard of using biopsy results. Of studies identified, evidence has been found with conflicting results. There is a need for well-designed trials to prove the clinical utility of this testing. The evidence is insufficient to prove an improvement in net health outcomes for this technology.

Practice Guidelines and Position Statements

American Gastroenterological Association (AGA)

In 2013, the AGA issued the following position statement on the diagnosis and management of celiac disease:

Many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optimal detection of patients.

North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)

In 2016, NASPGHAN issued the following guideline on the diagnosis and treatment of celiac disease in children:

To screen patients for celiac disease (CD), measurement of the immunoglobulin A (IgA) tissue transglutaminase antibody is the preferred test. Total serum IgA level should be measured to exclude selective IgA deficiency and to avoid false-negative test results. Patients with positive serologic test results should be referred to a gastroenterologist for endoscopic small intestinal biopsies to confirm the diagnosis. Testing for human leukocyte antigens DQ2 and DQ8 can help exclude the diagnosis. A gluten-free diet should not be started before confirming the diagnosis of CD. Serologic testing is very useful for screening patients with suspected CD. Early diagnosis is essential to prevent complications of CD.

National Institutes of Health (NIH)

According to a 2004 NIH Consensus Panel Statement on celiac disease, serological testing is the first step in pursuing a diagnosis of CD. The Consensus Statement said that the best available tests are the IgA anti-human tissue transglutaminase (TTG) and anti-endomesial IgA antibodies (EMA). According to the NIH Consensus Statement, the antigliadin IgA and IgG antibody tests are no longer routinely recommended because of their lower sensitivity and specificity.

The European Society of Pediatric Gastroenterology and Nutrition

The European Society of Pediatric Gastroenterology and Nutrition has established criteria for definitive diagnosis of CD. In children younger than two years of age, the criteria state diagnosis would be made only when reintroduction of gluten into the diet, after the intestinal mucosa has become normal, causes the mucosa again to become abnormal, with or without symptoms. In children older than two years of age, the criteria state a second challenge with gluten is not required if the initial biopsy is positive.

U.S. Preventive Services Task Force Recommendations

Not applicable.


Celiac disease, CD, celiac sprue, serologic tests, DGP, deamidated gliadin peptide, tTG, tissue transglutaminase, AGA, antigliadin antibodies, EMA, antiendomysial antibodies


This testing is approved by the United States FDA.


Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity


CPT codes:


Gammaglobulin; IgA, IgD, IgG, IgM, each


Immunoassay for analyte other than infectious agent antibody or infectious agent antigen, qualitative or semiquantitative; multiple step method


Immunoassay for analyte other than infectious agent antibody or infectious agent antigen, qualitative or semiquantitative; single step method (e.g., reagent strip)


Immunoassay, analyte, quantitative; not otherwise specified


Endomysial antibody (EMA), each immunoglobulin (Ig) class (Effective 01/01/22)


Fluorescent noninfectious agent antibody; screen, each antibody


Fluorescent noninfectious agent antibody; titer, each antibody


Gliadin (deamidated) (DGP) antibody, each immunoglobulin (Ig) class (Effective 01/01/22)


Tissue transglutaminase, each immunoglobulin (Ig) class (Effective 01/01/22)


HLA typing; DR/DQ, Single Antigen


Immunofluorescence, per specimen; initial single antibody stain procedure


each additional single antibody stain procedure (List separately in addition to code for primary procedure)


  1. Alessio MG TE, Brusca I, et al. Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease. J Pediatr Gastroenterol Nutr 2012; 55(1):44-49.
  2. American Gastroenterological Association Medical Position Statement: Celiac sprue. Gastroenterology 2001; 120(6): 1522-5.
  3. American Gastroenterological Association. AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131: 1977-1980.
  4. Basso D, Guariso G, Bozzato D et al. New screening tests enrich anti-transglutaminase results and support a highly sensitive two-test based strategy for celiac disease diagnosis. Clin Chim Acta 2011; 412(17-18):1662-7.
  5. Catassi C, Kryszak D, et al. Detection of Celiac disease in primary care: A multicenter case-finding study in North America. Am J Gastroenterol, July 2007; 102(7): 1454-1460.
  6. Farrell RJ and Kelly CP. Current concepts: Celiac sprue. N Engl J Med 2002; 346(3); 180-8.
  7. Farrell R, et al. Diagnosis of celiac sprue. Am J of Gastroenterology 2001; 96(12): 3237-46.
  8. Fasano A and Catassi C. Current approaches to diagnosis and treatment of celiac disease: An evolving spectrum. Gastroenterology 2001; 120(3): 636-51.
  9. Foucher B, Johanet C, Jego-Desplat S et al. Are Immunoglobulin A anti-gliadin antibodies of any help in the diagnosis of coeliac disease in children below 2 years-old? a French multicenter study. J Pediatr Gastroenterol Nutr 2012; 54(1):110-2.
  10. Green PH, Cellier C. Celiac disease. NEJM, October 25, 2007; 357: 1731-1743.
  11. Hill ID. What are the sensitivity and specificity of serologic tests for celiac disease? Do sensitivity and specificity vary in different populations? Gastroenterology, April 2005; 128(4 Suppl 1): S25-32.
  12. Hill ID, Dirks MH, Liptak GS et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005; 40(1):1-19.
  13. Hojsak I, Mozer-Glassberg Y, Segal Gilboa N et al. Celiac Disease Screening Assays for Children Younger than 3 Years of Age: The Performance of Three Serological Tests. Dig Dis Sci 2011.
  14. Hopper AD, Hadjivassiliou M, Hurlstone DP et al. What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis. Clin Gastroenterol Hepatol 2008; 6(3):314-20.
  15. Husby S, Koletzko S, Korponay-Szabó IR, et al; ESPGHAN Working Group on Coeliac Disease Diagnosis; ESPGHAN Gastroenterology Committee; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136-160.
  16. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  17. Katz KD, Rashtak S, Lahr BD et al. Screening for celiac disease in a North American population: sequential serology and gastrointestinal symptoms. Am J Gastroenterol 2011; 106(7):1333-9.
  18. Kelly, Ciaran P. (2018). Diagnosis of celiac disease in adults. In Grover, Shilpa (Ed.), UpToDate. Retrieved September 14, 2018 from
  19. Korponay-Szabo IR, Szabados K, Pusztai J et al. Population screening for coeliac disease in primary care by district nurses using a rapid antibody test: diagnostic accuracy and feasibility study. BMJ 2007; 335(7632):1244-7.
  20. Lagerqvist C, Dahlbom I, Hansson T et al. Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age. J Pediatr Gastroenterol Nutr 2008; 47(4):428-35.
  21. Lewis NR, Scott BB. Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease. Aliment Pharmacol Therap 2010; 31(1):73-81.
  22. Mubarak A WV, Gmelig-Meyling FH, et al. Tissue transglutaminase levels above 100 U/ml and celiac disease: a prospective study. World J Gastroenterol 2012; 18(32):4399-403.
  23. Mubarak A, Gmelig-Meyling FH, Wolters VM et al. Immunoglobulin G antibodies against deamidated-gliadin-peptides outperform anti-endomysium and tissue transglutaminase antibodies in children <2 years age. APMIS 2011; 119(12):894-900.
  24. Naiyer AJ, Hernandez L, Ciaccio EJ et al. Comparison of commercially available serologic kits for the detection of celiac disease. J Clin Gastroenterol 2009; 43(3):225-32.
  25. NIH consensus development conference on celiac disease. Consensus development conference statement. 2004. Available online at: Last accessed March 2010.
  26. Panetta F, Torre G, Colistro F et al. Clinical accuracy of anti-tissue transglutaminase as screening test for celiac disease under 2 years. Acta Paediatr 2011; 100(5):728-31.
  27. Pietzak A, et al. Celiac disease: Going against the grain. Nutrition in Clinical Practice 2001; 16:335-44.
  28. Rashid, M, Lee, J. Serologic testing in celiac disease; practical guide for clinicians. Can Fam Physician. 2016 Jan; 62(1): 38–43.
  29. Rashtak S, Ettore MW, Homburger HA, Murray JA. Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin Gastroenterol Hepatol. 2008 Apr;6(4):426-32; quiz 370. Epub 2008 Mar 4.
  30. Rubio-Tapia, Alberto, MD; Hill, Ivor D, MD; Kelly, Ciarán P, MD; Calderwood, Audrey H, MD; Murray, Joseph A, MD. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease. American Journal of Gastroenterology: May 2013:Volume 108:Issue 5:p.656–676
  31. Sblattero D, et al. Human recombinant tissue transglutaminase ELISA: An innovative diagnostic assay for celiac disease. Am J of Gastroenterology 2000; 95(5): 1253-57.
  32. Sugai E, Moreno ML, Hwang HJ et al. Celiac disease serology in patients with different pretest probabilities: is biopsy avoidable? World J Gastroenterol 2010; 16(25):3144-52.
  33. Vermeersch P, Geboes K, Marien G et al. Diagnostic performance of IgG anti-deamidated gliadin peptide antibody assays is comparable to IgA anti-tTG in celiac disease. Clin Chim Acta 2010; 411(13-14):931-5.
  34. Walburga D, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998; 115:1317-21.
  35. Walker-Smith JA GS, Schmitz J et al. Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child 1990; 65(8):909-11.
  36. Zanini B, Lanzarotto F, Mora A, Bertolazzi S, Turini D, Cesana B, Donato F, Ricci C, Lonati F, Vassallo F, Scarcella C, Lanzini A. Five year time course of celiac disease serology during gluten free diet: results of a community based "CD-Watch" program. Dig Liver Dis. 2010;42(12):865. Epub 2010 Jul 2.
  37. Zintzaras E and Germenis AE. Performance of antibodies against tissue transglutaminase for the diagnosis of celiac disease: Meta-analysis. Clinical and Vaccine Immunology, February 2006, vol. 13, No. 2, pp. 187-192.


Medical Policy Group, May 2004

Medical Policy Administration Committee, June 2004 (2)

Available for comment June 28-August 11, 2004

Medical Policy Group, May 2007 (1)

Medical Policy Group, November 2008 (2)

Medical Policy Group, February 2009 (1)

Medical Policy Administration Committee, March 2009

Available for comment March 4-April 17, 2009

Medical Policy Group, September 2010 (1)

Medical Policy Group, January 2012 (1): Update to Key Points and References related to MPP update; no change in policy statement

Medical Policy Panel, January 2013

Medical Policy Group, September 2013 (1): Deaminated gliadin peptide antibodies are considered investigational and verbiage is added to policy statement, rest of policy statement reconfigured for clarification purposes, along with the addition of tissue transglutaminase to coverage criteria; addition of CPT codes 81377, 81382 and 81383 related to genetic testing for HLA-DQ2/8; update to Key Points and References

Medical Policy Administration Committee, September 2013

Available for comment September 19 through November 2, 2013

Medical Policy Group, January 2014 (1): Removed all aspects of HLA-DQ testing related to celiac disease and created new policy #545; no other changes noted to policy

Medical Policy Group, November 2015: 2016 Annual Coding Update. Add CPT code 88346 and new CPT code 88350 to the current coding section and moved CPT code 88347 to previous coding.

Medical Policy Group, January 2014:  Effective 1/1/14: Active policy but no longer scheduled for regular literature reviews or updates.

Medical Policy Group, September 2018 (9): Updates to Key Points, References, Key Words. No change to policy statement.

Medical Policy Group, June 2019 (9): Updates to Description, Key Points, References. Added AGA and DGP abbreviations for clarification purposes to policy statement; no change to intent.

Medical Policy Group, May 2021 (9): Updates to Description, Key Points, References. Policy statement updated to remove “not medically necessary,” no change to policy intent. Corrected spelling of Key Word to gliadin.

Medical Policy Group, October 2021 (9): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, November 2021 (9): 2022 Annual Coding Update. Added CPT codes 86231, 86258, 86364 to the Current coding section.

Medical Policy Group, May 2022 (9): Updated Description. Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.