What Tissue Transglutaminase IgA Tells You
Tissue transglutaminase IgA (tTG-IgA) is the primary screening test for celiac disease, indicating the presence of autoantibodies against tissue transglutaminase-2, the major autoantigen in celiac disease. 1, 2
Diagnostic Significance
tTG-IgA has high sensitivity (90-96% in adults, 97.7% in children) and specificity (87.4% in adults at 15 U/mL threshold, 70.2% in children at 20 U/mL threshold) for detecting celiac disease 3, 2
The test performs better at ruling out celiac disease than ruling it in, due to specificity being lower than sensitivity 3
A positive tTG-IgA result strongly suggests celiac disease, particularly when levels exceed 10× the upper limit of normal, which correlates with severe intestinal damage and high likelihood of significant villous atrophy 3
The concordance rate between tTG-IgA and endomysial antibodies (EMA) is approximately 95-100% in untreated celiac disease 1, 4, 5
Clinical Context Required
Testing must be performed while the patient is on a gluten-containing diet to avoid false negative results 1, 3, 2
Total IgA levels must be measured concurrently, as IgA deficiency (occurring in 1-3% of celiac disease patients) causes falsely low tTG-IgA results 3, 2
If IgA deficiency is present, IgG-based assays (IgG deamidated gliadin peptide or IgG tTG) should be used instead 3
Interpretation Algorithm
For positive tTG-IgA results:
Confirm with endomysial antibody (EMA) testing, which has higher specificity (99.6% in adults, 93.8% in children) and helps rule in celiac disease 1, 3
Proceed to upper endoscopy with small bowel biopsy (at least 6 specimens from second part of duodenum) as the gold standard for diagnosis 1, 3, 2
HLA-DQ2/DQ8 testing has limited diagnostic value and is primarily useful for its negative predictive value to rule out celiac disease 1, 3
For discordant results (positive tTG-IgA, negative EMA):
This may represent early or developing celiac disease 3
Upper endoscopy with biopsy remains necessary to establish diagnosis 3
Monitoring Treatment Response
tTG-IgA levels typically decline within months of starting a gluten-free diet, with most significant drops occurring in the first year 3, 6
Follow-up testing schedule: at 6 months after starting gluten-free diet, at 12 months, then annually 3
Persistently elevated tTG-IgA levels despite dietary treatment suggest ongoing gluten exposure or poor dietary compliance 3, 6
Different tTG-IgA assays have varying sensitivity for detecting suboptimal treatment response—chemiluminescence immunoassays (CLIA) appear more sensitive than fluorochrome-enzyme immunoassays (FEIA) in detecting ongoing intestinal damage 7
Critical Pitfalls to Avoid
Never start a gluten-free diet before completing diagnostic workup, as this leads to false negative serology and inconclusive biopsies 3
Do not rely solely on serology without biopsy confirmation, especially with discordant results 3
Be aware of significant interlaboratory variability in absolute tTG-IgA values (median 50% variability), though qualitative interpretation (positive vs. negative) shows good agreement 8
In patients on gluten-free diet, switching between different tTG-IgA assays can produce discrepant results due to varying sensitivity thresholds 7