Anti-Gliadin Antibody Optimal Testing Recommendations

  • Antibodies against native gliadin are not recommended for the detection of celiac disease (CD). The AGA test has a low diagnostic accuracy and is considered outdated.
  • Immunoglobulin A (IgA) anti-tissue transglutaminase (tTG) antibody is the preferred single test for the serologic diagnosis of CD in individuals over the age of 2 years. The IgA anti-TTG test has 95% or higher sensitivity and specificity for CD.
  • Recently, tests for antibodies against the deamidated peptide of gliadin (DGP) have replaced the classic AGA test. Anti-DGP assays carry a considerably higher diagnostic accuracy than the old AGA assays, especially in the IgG class, and can substitute for anti-tTG tests in patients with selective IgA deficiency.
  • When a high probability of CD exists, the possibility of IgA deficiency should be considered and total IgA measured.
  • An alternative approach is to include both IgA- and IgG-based testing in high probability patients. The combination of IgA anti-tTG and IgG anti-DGP assays show greater sensitivity than a single test, with very high specificity.
  • In patients with low IgA levels or selective IgA deficiency, IgG-based testing (IgG anti-DGPs and IgG anti-tTG) should be performed.
  • All diagnostic serologic testing should be done in patients on a gluten-containing diet.
  • Screening of asymptomatic adults, adolescents, and children is not recommended.

Guidelines for Test Utilization

What does the test tell me?

Prior to the development of anti-tTG and anti-DGP tests, AGA and anti-endomysial antibody tests were preferred for the serologic diagnosis of CD.

When should I order this test?

The old AGA test should no longer be used. The updated assay, anti-DGP, when used in combination with anti-tTG, has excellent diagnostic sensitivity and specificity.

When should I NOT order this test?

Do not order this test. Order anti-tTG and anti-DGP tests instead. Using AGA results in lower diagnostic accuracy and unnecessary costs.

How should I interpret the result?

AGA testing is no longer indicated. It was used in the diagnosis of CD.

Is the test result diagnostic/confirmatory of the condition?

No, the AGA has been replaced by newer serologic tests (above). If the suspicion of CD is high, intestinal biopsy should be pursued even if serologies are negative. Familial occurrence and genetic influence in the pathogenesis of CD has been recognized. Alleles that encode human leukocyte antigen DQ2 or DQ8 proteins are present in most patients with CD. If biopsy and serology results disagree, HLA DQ2 and DQ8 genotyping is recommended.

Are there factors that can affect the lab result?

IgA deficiency may result in false negative IgA anti-tTG and IgA anti-DGP tests.

Are there considerations for special populations?

Not recommended for pediatric patients.

When testing children younger than 2 years of age for CD, the IgA anti-tTG test should be combined with anti-DGP (IgA and IgG).

What other test(s) might be indicated?

IgA anti-tTG and IgG anti-DGP

Intestinal biopsy, if the serologies are negative

References

Rubio-Tapia A, et al. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. 2013; 108:656-76.

Snyder MR, and Murray JA. Celiac disease: advances in diagnosis. Expert Rev Clin Immunol. 2016;12(4):449-63.

Screening for Celiac Disease: USPSTF recommendation statement. Am Family Phys. 2017; 96:392.



Last reviewed: June 2020. The content for Optimal Testing: AACC's Guide to Lab Test Utilization has been developed and approved by the AACC Academy and AACC's Science and Practice Core Committee.

As the fields of laboratory medicine and diagnostic testing continue to grow at an incredible rate, the knowledge and expertise of clinical laboratory professionals is essential to ensure that patients received the highest quality and most useful laboratory tests. AACC's Academy and Science and Practice Core Committee have developed a test utilization resource focusing on commonly misused tests in hospitals and clinics. Improper test utilization can result in poor patient outcomes and waste in the healthcare system. This important resource geared toward medical professionals recommends better tests and diagnostic practices. Always consult your laboratory director to make sure these recommendations are appropriate for your patient population.