What does tissue transglutaminase (tTG) Immunoglobulin A (IgA) indicate?

Tissue Transglutaminase IgA in Celiac Disease Diagnosis

Tissue transglutaminase IgA (tTG-IgA) is the primary serological marker for celiac disease with high sensitivity (90-96% in adults, 97.7% in children) and specificity (87.4% in adults, 70.2% in children), serving as the first-line test for celiac disease screening. 1

Diagnostic Significance of tTG-IgA

Primary Diagnostic Role

• tTG-IgA detects antibodies against tissue transglutaminase, the main autoantigen in celiac disease 1
• Positive results strongly suggest celiac disease, especially when levels are significantly elevated 2
• Threshold values of 15 U/mL for adults and 20 U/mL for children are commonly used 2

Diagnostic Performance

• In adults: 90.7% sensitivity, 87.4% specificity at 15 U/mL threshold 2
• In children: 97.7% sensitivity, 70.2% specificity at 20 U/mL threshold 2
• Higher sensitivity than IgA endomysial antibodies (EMA) but lower specificity 2

Testing Protocol

Critical Testing Considerations

1. Always check total serum IgA simultaneously to rule out IgA deficiency (present in 1-3% of celiac patients) 2, 1
2. Patient must maintain regular gluten consumption (1-3 slices of bread daily) for at least 6 weeks prior to testing 1
3. False negatives can occur in:
   • IgA deficiency
   • Patients already on gluten-free diet
   • Children under 2 years of age 3

Confirmatory Testing

• Positive tTG-IgA should be confirmed with:
  • IgA endomysial antibodies (EMA) - 88% sensitivity in adults, 94.5% in children, with extremely high specificity (99.6% in adults) 2, 1
  • Small bowel biopsy (gold standard) - at least 6 samples from duodenal bulb and distal duodenum 1

Interpretation of Results

Positive tTG-IgA

• Strongly suggests celiac disease, especially with symptoms
• Requires confirmation with small bowel biopsy before starting gluten-free diet 2, 1
• Higher values correlate with greater intestinal damage 2

Negative tTG-IgA

• Generally rules out celiac disease (high negative predictive value) 4
• Exception: IgA deficiency - requires IgG-based testing (IgG-DGP or IgG-tTG) 1

Special Considerations

• Different tTG-IgA assays may show varying sensitivity in monitoring treatment response 5
• Chemiluminescence immunoassays (CLIA) appear more sensitive than fluorochrome-enzyme immunoassays (FEIA) for detecting suboptimal treatment response 5

Clinical Applications

Screening High-Risk Populations

• Type 1 diabetes patients (5.4% have positive tTG-IgA) 2
• First-degree relatives of celiac patients
• Patients with other autoimmune disorders

Monitoring Treatment Response

• tTG-IgA levels typically decrease after starting gluten-free diet
• Should be tested at 6 and 12 months after diagnosis, then yearly 1
• Persistently elevated levels suggest ongoing gluten exposure or poor diet adherence 5

Pitfalls and Limitations

• Premature gluten restriction before testing can lead to false negatives 1
• IgA deficiency causes false negatives with IgA-based tests 2, 1
• Isolated positive IgG-tTG with negative tTG-IgA has low diagnostic utility (3%) in non-IgA deficient patients 1
• Different commercial assays may have varying performance characteristics 5

By following this structured approach to tTG-IgA testing and interpretation, clinicians can effectively screen for and monitor celiac disease, leading to improved outcomes through early diagnosis and proper management.