Testing for Celiac Disease
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Intestinal biopsy is the gold standard for diagnosing celiac disease, but serologic tests provide an effective first step in identifying biopsy candidates. In addition, genetic tests that confirm the presence or absence of specific genes associated with celiac disease may be useful in some circumstances. However, serologic and genetic tests are adjuncts to, not replacements for, biopsies. If serologic or genetic tests indicate the possibility of celiac disease, a biopsy should be done promptly and before initiating any change in the patient’s diet.
Serologic Tests
Serologic tests look for three antibodies common in celiac disease:
- anti-tissue transglutaminase (tTG) antibodies
- endomysial antibodies (EMA)
- antigliadin antibodies (AGA)
The most sensitive antibody tests are of the immunoglobulin A (IgA) class, but immunoglobulin G (IgG) tests may be used in patients with IgA deficiency. Because no one serologic test is ideal, panels are often used. However, the tests included in a celiac panel vary by lab and may include one or more that are unwarranted. The American Gastroenterological Association recommends beginning with tTG in the clinical setting.1
For accurate diagnostic test results, patients must be on a gluten-containing diet.
1American Gastroenterological Association. AGA Institute medical position statement on the diagnosis and management of celiac disease. Gastroenterology. 2006;131:1977–1980.
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tTG Antibody
The tTG test is an enzyme-linked immunosorbent assay (ELISA) test. The tTG test has a sensitivity of more than 90 percent, yielding few false negative results. The test also has a specificity of more than 95 percent, meaning it yields few false postive results.1 Point-of-care tTG tests have been developed but are not yet approved for use by clinicians in the United States.
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EMA
The test for EMA is slightly less sensitive than tTG but is highly specific for celiac disease, approaching 100 percent accuracy.2 EMA is measured by indirect immunofluorescent assay, a more expensive and time-consuming process than ELISA testing. In addition, the EMA test is subject to operator interpretation, making the results more subjective than those for tTG.
Some studies show the titers, or relative concentrations, of tTG and EMA are correlated with the degree of intestinal damage, making these tests less sensitive among patients with milder celiac disease.3
2Green PHR, Cellier C. Medical progress: celiac disease. The New England Journal of Medicine. 2007;357:1731–1743.
3Tursi A, Brandimarte G, Giorgetti GM. Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease. Journal of Clinical Gastroenterology. 2003;36(3):219–221.
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AGA
Tests for AGA are not sensitive or specific enough for routine use. However, they may be useful for screening children younger than 18 months old in whom tTG and EMA tests may yield false negative results.2
A new generation of tests that use deaminated gliadin peptides (DGP) have sensitivity and specificity that are substantially better than the older gliadin tests.4 DGP tests are more accurate than tTG and AGA and may be the most reliable tests to detect celiac disease in people with IgA deficiency.
4Rashtak S, Ettore MW, Homburger HA, Murray JA. Combination testing for antibodies in the diagnosis of celiac disease: comparison of multiplex immunoassay and ELISA methods. Alimentary Pharmacology & Therapeutics. 2008;28(6):805–813.
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IgA Deficiency
Between 2 and 3 percent of celiac patients have selective IgA deficiency—a rate about 10 times higher than in the general population. If IgA tTG or IgA EMA are negative but celiac disease is still suspected, total IgA should be measured to identify selective IgA deficiency. In cases of IgA deficiency, IgG tTG or DGP-IgG should be measured.
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Genetic Screening Tests
Nearly all people with celiac disease have gene pairs that encode for at least one of the human leukocyte antigen (HLA) gene variants, or alleles, designated HLA-DQ2 or HLA-DQ8. However, these alleles are common. They are found in about 40 percent of the general U.S. population, and most people with these alleles do not have celiac disease. Negative findings for HLA-DQ2 and HLA-DQ8 can essentially rule out current or future celiac disease in patients for whom other tests, including biopsy, do not provide a clear diagnostic result.
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Acknowledgments
Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts. This publication was reviewed by Alessio Fasano, M.D., University of Maryland School of Medicine, and Joseph A. Murray, M.D., Mayo Clinic, Rochester, MN.
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The Celiac Disease Awareness Campaign
The National Institutes of Health Celiac Disease Awareness Campaign provides current, comprehensive, science-based information about the symptoms, diagnosis, and treatment of celiac disease, also known as celiac sprue, nontropical sprue, and gluten-sensitive enteropathy. The Awareness Campaign is an initiative of the National Digestive Diseases Information Clearinghouse, a service of the National Institute of Diabetes and Digestive and Kidney Diseases.
Download this publication and learn more about the Awareness Campaign at www.celiac.nih.gov.
Celiac Disease Awareness Campaign
c/o National Digestive Diseases Information Clearinghouse
2 Information Way
Bethesda, MD 20892–3570
Phone: 1–800–891–5389
TTY: 1–866–569–1162
Fax: 703–738–4929
Email: nddic@info.niddk.nih.gov
Internet: www.digestive.niddk.nih.gov
The National Digestive Diseases Information Clearinghouse (NDDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health of the U.S. Department of Health and Human Services. Established in 1980, the Clearinghouse provides information about digestive diseases to people with digestive disorders and to their families, health care professionals, and the public. The NDDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about digestive diseases.
This publication is not copyrighted. The Clearinghouse encourages users of this publication to duplicate and distribute as many copies as desired.
This publication may contain information about medications. When prepared, this publication included the most current information available. For updates or for questions about any medications, contact the U.S. Food and Drug Administration toll-free at 1–888–INFO–FDA (1–800–463–6332) or visit www.fda.gov. Consult your health care provider for more information.
NIH Publication No. 09–7351
April 2009
Page last updated May 10, 2012
