Celiac Disease Tests
Health care professionals most often use serologic tests and intestinal biopsies to diagnose celiac disease. If serologic tests suggest that a patient could have celiac disease, health care professionals should then order intestinal biopsies to confirm the diagnosis.
Genetic tests that confirm the presence or absence of specific genes associated with celiac disease may be beneficial in some cases.
Ordering serologic tests—blood tests that check for antibodies—is typically the first step in diagnosing celiac disease.
Serologic tests for celiac disease include
- tissue transglutaminase (tTG) immunoglobulin A (IgA) and tTG immunoglobulin G (IgG) tests
- endomysial antibody (EMA) -IgA test
- deamidated gliadin peptide (DGP) -IgA and DGP-IgG tests
The serologic tests that check for IgA antibodies are more sensitive for celiac disease than the tests for IgG antibodies. However, in people who have IgA deficiency, IgG tests may be useful. For accurate diagnostic test results, a patient must be eating a diet that contains gluten.
Celiac panels that include a combination of serologic tests are available. The tests included in a panel vary by lab, and all of the tests may not be necessary. Some labs have developed cascades of tests to avoid automatically running unnecessary tests. Point-of-care serologic tests for celiac disease have been developed. However, more research on the accuracy of point-of-care tests is needed.
In addition to using serologic tests to help diagnose celiac disease, health care professionals may use them to monitor how well patients are following a gluten-free diet.
tTG-IgA and tTG-IgG tests
The tTG-IgA test is the preferred celiac disease serologic test for most patients.1 Research suggests that the tTG-IgA test has a sensitivity of 78% to 100% and a specificity of 90% to 100%.2 The performance of this test may depend on the degree of intestinal damage, making the test less sensitive in patients who have mild celiac disease. The test may also be less sensitive in children younger than age 2.1 The tTG-IgA test is most often an enzyme-linked immunosorbent assay (ELISA).
Health care professionals may order the tTG-IgG test to help diagnose celiac disease in patients who have IgA deficiency. The tTG-IgG test is not useful in other circumstances.
Health care professionals may use the EMA-IgA test after the tTG-IgA test to help make a diagnosis of celiac disease more certain. Research suggests that the EMA-IgA test has a sensitivity of 86% to 100% and a specificity of 97% to 100%.2 The performance of this test may depend on the degree of intestinal damage, making the test less sensitive in patients who have mild celiac disease. The test may also be less sensitive in children younger than age 2.1
The EMA-IgA test is an immunofluorescent assay that is more expensive and time-consuming to perform than the tTG-IgA test. The EMA-IgA test is also qualitative, making the results more subjective than tTG-IgA test results.
DGP-IgA and DGP-IgG tests
The DGP tests are less sensitive and specific than the tTG-IgA test.3 However, health care professionals may order DGP tests in certain circumstances. For example, because tTG and EMA tests may be less sensitive in infants and young children, some experts recommend combining the DGP tests with the tTG-IgA test in children younger than age 2.1 For patients with IgA deficiency, health care professionals may order the DGP-IgG test.
Although only 1 in 400 to 1 in 800 people in the general population have IgA deficiency, 2% to 3% of people with celiac disease have IgA deficiency.1 In patients with IgA deficiency, IgA-based tests—such as tTG-IgA—may not accurately detect celiac disease, and IgG-based tests can help with diagnosis.
If a tTG-IgA or EMA-IgA test result is negative in a patient with suspected celiac disease, health care professionals may order a total IgA test, a serology test for IgA deficiency.
For patients with a high chance of having celiac disease who could be IgA deficient, health care professionals may order the total IgA and tTG-IgA tests at the same time. Health care professionals may also order an IgA-based test and an IgG-based test at the same time to check for both types of antibodies. However, if the tTG-IgG alone is positive, and the patient does not have IgA deficiency, then the tTG-IgG test is rather inaccurate.
Some laboratories have designed a cascade of tests that starts with the total IgA measurement. If the level is normal, tTG-IgA is measured. If the total IgA is low, then both tTG-IgA and tTG-IgG are measured. If the total IgA is deficient, only the tTG-IgG and often the DGP-IgG are measured. This strategy avoids using the tTG-IgG test, which is often falsely positive.
Note that if the total IgA is undetectably low, this suggests that the patient may have an immunoglobulin deficiency disorder, the most common type being selective IgA deficiency. Further evaluation may be needed.
If serologic tests suggest that a patient could have celiac disease, health care professionals should order an upper GI endoscopy with biopsies of the duodenum—including the duodenal bulb and distal duodenum—to confirm the diagnosis.
In some circumstances, if upper GI endoscopy is not feasible, a reliable diagnosis of celiac disease can be made if the initial blood sample has a very strongly positive tTG-IgA result that is greater than 10 times the upper limit of normal, and a subsequent blood sample has a positive EMA-IgA. However, this practice has not been endorsed in adult gastroenterology as yet.
If a patient’s serologic test results are negative and a health care professional still suspects celiac disease, a health care professional may order intestinal biopsies to check for celiac disease or what could be another cause for a patient’s symptoms. About 2% to 3% of patients with celiac disease have negative serologic test results.4
People with celiac disease almost always have at least one of two groups of human leukocyte antigen (HLA) gene variants that encode the following serotype equivalents: HLA-DQ2.5 or HLA-DQ8. About 95% of people with celiac disease have HLA-DQ2.5.1 Among the other 5%, most have HLA-DQ8.1 A very small percentage have other genetic variants, such as DQ2.2, which are very rarely associated with celiac disease.
However, about 30% of the general population has HLA-DQ2.5 or HLA-DQ8, and only about 3% of people with these gene variants develop celiac disease.4
Genetic testing for HLA-DQ2.5 and HLA-DQ8 may help rule out celiac disease in certain circumstances. For example, health care professionals may order genetic tests in patients for whom other tests do not provide a clear diagnostic result. If a patient’s genetic test results are negative for HLA-DQ2.5 and HLA-DQ8, he or she is very unlikely to have, or to develop, celiac disease.
 Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. American Journal of Gastroenterology. 2013;108(5):656–677. doi:10.1038/ajg.2013.79
 Hujoel IA, Reilly NR, Rubio-Tapia A. Celiac disease: clinical features and diagnosis. Gastroenterology Clinics of North America. 2019;48(1):19–37. doi:10.1016/j.gtc.2018.09.001
 Husby S, Murray JA, Katzka DA. AGA clinical practice update on diagnosis and monitoring of celiac disease—changing utility of serology and histologic measures: expert review. Gastroenterology. 2019;156(4):885–889. doi:10.1053/j.gastro.2018.12.010
 Celiac disease. National Library of Medicine, MedlinePlus. Updated April 2019. Accessed December 1, 2020. https://medlineplus.gov/genetics/condition/celiac-disease.
This content is provided as a service of the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), part of the National Institutes of Health. The NIDDK translates and disseminates research findings to increase knowledge and understanding about health and disease among patients, health professionals, and the public. Content produced by the NIDDK is carefully reviewed by NIDDK scientists and other experts.
The NIDDK would like to thank:
Joseph A. Murray, M.D., Mayo Clinic