The Primary Serum Test for Celiac Disease
The primary serum test for celiac disease is the tissue transglutaminase IgA antibody (tTG-IgA) test. 1
Diagnostic Testing Algorithm for Celiac Disease
First-Line Testing
- tTG-IgA antibody test is the preferred initial serological test for individuals over 2 years of age due to its:
- Total serum IgA level should be measured simultaneously to rule out IgA deficiency 1, 2
Special Populations
- For children under 2 years: Combine tTG-IgA with IgG and IgA deamidated gliadin peptide antibodies 2
- For IgA-deficient patients: Use IgG-based testing including:
Confirmatory Testing
- Endomysial antibody (EMA-IgA) test is recommended as a second-line confirmatory test when:
- tTG-IgA results are weakly positive
- Additional confirmation is needed 1
- EMA testing has slightly lower sensitivity but higher specificity than tTG-IgA 1, 3
Critical Testing Considerations
Testing Requirements
- Patient must be on a gluten-containing diet for at least 6 weeks prior to testing 1, 2
- False negatives occur if testing is performed after starting a gluten-free diet 2
Interpreting Results
- High tTG-IgA levels (>10× upper limit of normal):
- Highly predictive of celiac disease
- When combined with positive EMA, has nearly 100% positive predictive value 1
- Borderline or weakly positive results should be followed with EMA testing 1
Diagnostic Confirmation
- Small intestinal biopsy remains the gold standard for diagnosis in adults 1, 2
- Multiple duodenal biopsies should be obtained during endoscopy 1, 2
Common Pitfalls to Avoid
Failing to check total IgA levels - IgA deficiency occurs in 1-3% of celiac patients and leads to false-negative tTG-IgA results 1
Testing after gluten restriction - Antibody levels decrease rapidly on a gluten-free diet, reducing test sensitivity 1, 4
Relying on at-home celiac tests - These have lower accuracy than laboratory-based tests and lack professional oversight 2
Using antibody tests alone to monitor treatment response - tTG-IgA and EMA-IgA have low sensitivity (<50%) for detecting persistent villous atrophy in patients on gluten-free diets 4
Using antigliadin antibodies as primary screening - These older tests have inferior accuracy compared to tTG-IgA and EMA-IgA 1
The development of the tTG-IgA test represented a significant advancement in celiac disease diagnosis, providing a highly accurate, automated alternative to the more labor-intensive EMA test, while targeting the same autoantigen 1, 5, 6.