Diagnostic Testing for Celiac Disease: IgA Tissue Transglutaminase Antibodies
The IgA tissue transglutaminase (tTG) antibody test is the preferred serological test for diagnosing celiac disease in individuals over two years of age. 1
Primary Testing Approach
- IgA tTG antibody testing is the most efficient single serologic test for detecting celiac disease in the primary care setting, with sensitivity of 90-96% and specificity greater than 95% 1, 2
- Testing must be performed while the patient is on a gluten-containing diet (at least 10g daily for 6-8 weeks) to avoid false-negative results 2, 3
- All diagnostic serologic testing should be completed before initiating a gluten-free diet 1
- Antibodies directed against native gliadin are no longer recommended for primary detection of celiac disease 1
Testing Algorithm
- Start with IgA tTG antibody as the initial screening test 1, 2
- If IgA tTG is positive, confirm with IgA endomysial antibody (EMA) testing, which has slightly lower sensitivity but excellent specificity (99.6%) 1
- Measure total IgA levels if celiac disease is strongly suspected despite negative IgA tTG results, or in patients with high probability of celiac disease and possible IgA deficiency 1
- In IgA-deficient patients, use IgG-based tests (IgG EMA, IgG deamidated gliadin peptide, or IgG tTG) which have excellent sensitivity and specificity in this population 1, 4
Special Considerations
- In children under two years of age, combine IgA tTG testing with IgG and IgA deamidated gliadin peptides to improve sensitivity 1
- For adults with weakly positive IgA tTG results, IgA EMA should be measured as a confirmatory test 1, 2
- Combining multiple tests instead of using IgA tTG alone may marginally increase sensitivity but reduces specificity and is not recommended in low-risk populations 1
- Positive serologic test results are supportive but not diagnostic of celiac disease; confirmation requires intestinal biopsy showing characteristic histologic changes 1
Interpretation of Results
- IgA tTG levels >10x the upper limit of normal have high positive predictive value (>98%) for celiac disease 3, 2
- Discordant results (positive tTG IgA, negative EMA) have a low rate of celiac disease (12%) compared to concordant positive results (85%) 5, 3
- The concordance rate between IgA tTG and IgA EMA is approximately 95% 6, 2
- Different tTG IgA assays may show varying rates of normalization in patients on gluten-free diets, with chemiluminescence immunoassays potentially being more sensitive for detecting suboptimal treatment response 7
Common Pitfalls
- Initiating a gluten-free diet before completing diagnostic testing can lead to false-negative results 2, 8
- Relying solely on serology without biopsy confirmation can lead to misdiagnosis 2, 3
- A normal tTG level does not necessarily predict recovery of villous atrophy in patients with celiac disease on a gluten-free diet 9, 7
- IgG isotype testing for tTG antibody is not specific in the absence of IgA deficiency 2, 4
- Seronegative celiac disease can occur and requires biopsy for diagnosis in patients with high clinical suspicion 3, 8
By following this evidence-based approach to serological testing for celiac disease, clinicians can effectively screen patients and guide appropriate follow-up diagnostic procedures to confirm the diagnosis.