What it measures.
Tissue transglutaminase IgA (tTG-IgA) is the recommended first-line serological test for celiac disease screening. It detects IgA antibodies against tissue transglutaminase 2, the autoantigen in celiac disease. With sensitivity of ~93% and specificity of ~95%, it is the most cost-effective celiac screening tool. Total IgA must always be checked simultaneously to rule out IgA deficiency, which causes false negatives.
IgA-class antibodies directed against tissue transglutaminase 2 (tTG2), an enzyme present in the intestinal subepithelial layer. In celiac disease, gliadin (from dietary gluten) is deamidated by tTG2, creating neoepitopes that trigger an adaptive immune response. The resulting anti-tTG IgA antibodies are highly specific for celiac disease.
Why it matters.
Celiac disease affects 1% of the population but up to 70% are undiagnosed. tTG-IgA allows mass screening without endoscopy. A negative result in an IgA-sufficient individual effectively rules out celiac disease. Very high tTG-IgA (>10x ULN) with positive EMA allows no-biopsy diagnosis in children (ESPGHAN 2020). The test also monitors dietary compliance — levels normalise within 6-12 months on a strict gluten-free diet.
Physiology.
When genetically susceptible individuals (HLA-DQ2/DQ8 positive) ingest gluten, gliadin peptides cross the intestinal epithelium and are deamidated by tissue transglutaminase 2. These deamidated peptides are presented by HLA-DQ2/DQ8 on antigen-presenting cells to CD4+ T cells, triggering an immune response that produces anti-tTG IgA antibodies and drives villous atrophy.
Testing & preparation.
How to prepare
- MUST be on a gluten-containing diet at time of testing
- If already gluten-free, a gluten challenge (6-8 weeks) is needed before testing
- No fasting required
- Total IgA MUST be ordered simultaneously to rule out IgA deficiency
- Biotin supplements do not interfere with this test
When to test
Suspected celiac disease (diarrhoea, bloating, iron deficiency). Family screening (first-degree relatives). Type 1 diabetes or autoimmune thyroid disease. Unexplained elevated liver enzymes. Unexplained osteoporosis. Infertility workup.
How often
Once for screening. At 6 and 12 months post-diagnosis for monitoring dietary compliance. Annually thereafter if clinically indicated.
Interpretation.
High tissue transglutaminase iga
Common causes:
- Celiac disease (most common and clinically significant cause)
- Dermatitis herpetiformis (cutaneous celiac disease)
- False positive: autoimmune liver disease, heart failure, some infections (uncommon)
Implications:
- Positive tTG-IgA → referral for duodenal biopsy to confirm diagnosis (ACG 2023 for adults)
- Very high (>10x ULN) + positive EMA → no-biopsy diagnosis acceptable in children (ESPGHAN 2020)
- Monitoring: falling tTG-IgA confirms gluten-free diet adherence; persistent elevation suggests ongoing gluten exposure
Low tissue transglutaminase iga
Common causes:
- No celiac disease (true negative)
- IgA deficiency causing false negative (check total IgA!)
- Already on gluten-free diet at time of testing (false negative)
- Very early or mild celiac disease (rare false negative, ~5-7%)
Implications:
- Negative tTG-IgA with normal total IgA → celiac disease effectively ruled out
- Negative tTG-IgA with low total IgA → order DGP-IgG or tTG-IgG instead
- If clinical suspicion remains high despite negative serology → discuss biopsy with gastroenterologist
Optimization.
Diet
- Strict gluten-free diet is the only intervention that lowers tTG-IgA in confirmed celiac disease
- Even small amounts of gluten maintain antibody production
- Cross-contamination from shared kitchens can prevent serological normalisation
Lifestyle
- Dietitian support is essential for gluten-free diet adherence
- Join a celiac disease support group for practical guidance
- Read labels carefully — gluten is hidden in many processed foods
Supplements
- No supplements lower tTG-IgA — only gluten elimination works
- Address nutritional deficiencies caused by celiac: iron, vitamin D, B12, folate, calcium
FAQs.
Why do I need to be eating gluten when tested?
tTG-IgA is produced in response to gluten exposure. On a gluten-free diet, antibody levels fall and the test becomes falsely negative. You must be consuming gluten for at least 6-8 weeks before testing for a reliable result.
What if my tTG-IgA is negative but my total IgA is low?
Selective IgA deficiency (present in 2-3% of celiac patients) makes all IgA-based tests unreliable. Your doctor should order IgG-based alternatives: tTG-IgG or deamidated gliadin peptide IgG (DGP-IgG). This is why total IgA must always be checked alongside tTG-IgA.
How long after starting a gluten-free diet should tTG-IgA normalise?
tTG-IgA typically falls to normal within 6-12 months of strict gluten-free diet adherence. If it remains elevated at 12 months, ongoing gluten exposure (intentional or cross-contamination) is the most common cause. Persistent elevation beyond 24 months warrants evaluation for refractory celiac disease.