Anti-Tissue Transglutamin (Anti-tTG)

Anti-tissue transglutaminase (anti-tTG) antibodies are the primary screening test for celiac disease — an autoimmune condition where gluten triggers the immune system to attack the small intestine. When people with celiac disease eat gluten (a protein in wheat, barley, and rye), their immune system produces antibodies against tissue transglutaminase, an enzyme in the intestinal lining. Detecting these antibodies provides a highly accurate, non-invasive way to screen for this common but underdiagnosed condition.

Celiac disease affects approximately 1% of the population, but studies suggest 80-90% of cases remain undiagnosed. Many patients have subtle or atypical symptoms that go unrecognized for years — the average time from symptom onset to diagnosis is 6-10 years. The condition causes intestinal damage that impairs nutrient absorption, leading to a wide range of complications including anemia, osteoporosis, infertility, and neurological problems. Anti-tTG testing enables early detection, allowing patients to start a gluten-free diet that heals the intestine and prevents these complications.

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Key Benefits of Testing

Anti-tTG testing provides highly accurate celiac screening with approximately 95% sensitivity and 95% specificity. This means it correctly identifies most people with celiac disease while rarely producing false positives, making it ideal as a first-line test before considering intestinal biopsy.

The test also serves an important role in monitoring diagnosed patients. Antibody levels decline on a strict gluten-free diet and rise with gluten exposure, helping assess whether patients are successfully avoiding gluten and whether their intestine is healing.

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What Does This Test Measure?

The anti-tTG test measures IgA antibodies directed against tissue transglutaminase (tTG), an enzyme found throughout the body but particularly important in the intestinal lining. In celiac disease, when gluten is eaten, the immune system mistakenly attacks this enzyme and produces detectable autoantibodies.

How Celiac Disease Triggers Anti-tTG

When a person with celiac disease eats gluten, the protein is partially digested into fragments called gliadin. These fragments cross the intestinal barrier and encounter tissue transglutaminase, which modifies them. The modified gliadin-tTG complexes are presented to the immune system by cells carrying specific HLA genes (HLA-DQ2 or HLA-DQ8, present in nearly all celiac patients). The immune system then produces antibodies against both the modified gliadin and the tTG enzyme — these anti-tTG antibodies are what the test detects.

IgA vs IgG Anti-tTG

Most testing uses IgA anti-tTG because it’s more specific for celiac disease. However, about 2-3% of celiac patients have IgA deficiency — their bodies don’t produce enough IgA antibodies of any kind. In these patients, IgA-based tests will be falsely negative. This is why testing should include total IgA level to identify IgA-deficient patients who need IgG-based celiac testing instead.

Anti-tTG vs Other Celiac Antibodies

Several antibodies can screen for celiac disease:

• Anti-tTG IgA: First-line screening; best combination of sensitivity and specificity
• Anti-endomysial antibodies (EMA): Highly specific confirmatory test; often used to verify positive anti-tTG
• Deamidated gliadin peptide (DGP): Useful in IgA deficiency and children under 2 years who may not yet produce anti-tTG

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Why This Test Matters

Detects Underdiagnosed Disease

Celiac disease is dramatically underdiagnosed. Many patients have non-classic symptoms — fatigue, anemia, bone loss — rather than obvious digestive problems. Some are told they have irritable bowel syndrome or other conditions. Anti-tTG testing identifies these missed cases, enabling treatment that transforms quality of life.

Prevents Serious Complications

Untreated celiac disease causes progressive intestinal damage and malabsorption leading to serious complications over time. These include iron deficiency anemia (from impaired iron absorption), osteoporosis (from impaired calcium and vitamin D absorption), other nutritional deficiencies (B12, folate, zinc), infertility and pregnancy complications, increased risk of intestinal lymphoma, and neurological problems including peripheral neuropathy and ataxia. Early detection and treatment with a gluten-free diet prevents these outcomes.

Screens At-Risk Groups

Certain groups have much higher celiac prevalence and benefit from screening even without symptoms. First-degree relatives of celiac patients have 10-15% risk (vs 1% general population). Type 1 diabetics have 3-10% celiac prevalence. Those with autoimmune thyroid disease, Down syndrome, Turner syndrome, or IgA deficiency also have elevated risk.

Value of Regular Monitoring

For diagnosed celiac patients, periodic anti-tTG testing tracks dietary compliance and intestinal healing. Antibody levels should decline on a strict gluten-free diet and eventually become negative. Persistently elevated antibodies indicate ongoing gluten exposure — either intentional or from inadvertent contamination — requiring dietary review.

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What Can Affect Test Results?

Causes of Positive Anti-tTG

Celiac disease is by far the most common cause — the antibody is highly specific. False positives occasionally occur with other autoimmune conditions (type 1 diabetes, autoimmune thyroid or liver disease), chronic liver disease, or heart failure. However, false positive rates are low, especially at higher antibody levels. Very high anti-tTG (more than 10 times the upper limit of normal) is highly specific for celiac disease.

Causes of False-Negative Anti-tTG

Gluten-free diet before testing is the most critical pitfall. Antibody levels decline within weeks to months of gluten elimination. Patients who self-start a gluten-free diet before testing may have falsely negative results, making diagnosis difficult.

IgA deficiency causes false negatives with IgA-based tests. If total IgA is low or absent, the test will be negative regardless of celiac status. Always check total IgA or order IgG-based tests in parallel.

Young children under 2 may not yet have developed anti-tTG antibodies even with celiac disease. DGP antibodies are more sensitive in this age group.

Early or mild disease occasionally produces antibody levels below the test threshold, though this is uncommon.

Critical Requirement: Must Be Eating Gluten

This point cannot be overstated: anti-tTG testing is only valid if the patient is actively consuming gluten. Guidelines recommend eating gluten-containing foods (equivalent to at least 1-2 slices of bread daily) for at least 6-8 weeks before testing. Patients who have already started a gluten-free diet should either undergo a gluten challenge or have testing performed before eliminating gluten.

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When Should You Get Tested?

GI symptoms suggesting celiac disease: Chronic or recurrent diarrhea, abdominal pain or bloating, unexplained weight loss, or fatty stools. However, many celiac patients have constipation rather than classic diarrhea, so absence of diarrhea doesn’t exclude celiac disease.

Non-GI manifestations that should prompt testing:

• Unexplained iron deficiency anemia (especially if unresponsive to supplementation)
• Unexplained osteoporosis or osteopenia, particularly in younger patients
• Dermatitis herpetiformis (intensely itchy blistering rash on elbows, knees, buttocks)
• Unexplained infertility or recurrent miscarriage
• Elevated liver enzymes without other explanation
• Peripheral neuropathy or ataxia without other cause
• Recurrent mouth ulcers or dental enamel defects
• Chronic fatigue

At-risk groups (screen even without symptoms):

• First-degree relatives of celiac patients (parents, siblings, children)
• Type 1 diabetes
• Autoimmune thyroid disease
• Down syndrome, Turner syndrome, Williams syndrome
• Selective IgA deficiency

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Understanding Your Results

Anti-tTG results are typically reported as a number with a reference range, or as positive/negative with a titer. Interpretation depends on the level and clinical context.

Negative anti-tTG: Celiac disease is unlikely if the patient was eating adequate gluten and has sufficient IgA. Always confirm total IgA was normal — if IgA is deficient, a negative result doesn’t rule out celiac and IgG-based tests are needed.

Weakly positive (less than 2-3 times upper limit): May indicate celiac but false positives are more common at lower titers. Confirmatory testing with EMA or DGP antibodies is recommended. Intestinal biopsy may be needed for definitive diagnosis.

Strongly positive (more than 10 times upper limit): Highly specific for celiac disease. In children with classic symptoms and very high anti-tTG confirmed by positive EMA, current guidelines allow diagnosis without biopsy. In adults, biopsy is still generally recommended to confirm diagnosis before committing to lifelong dietary treatment.

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What to Do About Abnormal Results

For Positive Results

Don’t start a gluten-free diet yet! This is critical — starting the diet before completing evaluation interferes with biopsy results and makes definitive diagnosis difficult. Continue eating gluten until workup is complete.

Confirm the finding with additional testing — EMA antibodies (highly specific) or DGP antibodies. Confirmatory testing is especially important for weakly positive results.

Referral to gastroenterology for endoscopy with duodenal biopsy is typically next. Biopsy confirms characteristic intestinal damage (villous atrophy) and provides baseline assessment of disease severity.

After confirmed diagnosis, start a strict gluten-free diet under guidance from a dietitian experienced in celiac disease. Screen for nutritional deficiencies (iron, B12, folate, vitamin D) and bone density. Screen first-degree relatives.

For Negative Results

Verify IgA sufficiency — check total IgA if not already done. If IgA is deficient, order IgG-based celiac tests.

Confirm gluten intake — if the patient was already on a reduced-gluten diet, results may be falsely negative. A gluten challenge followed by repeat testing may be needed.

Consider other diagnoses if celiac is ruled out. Symptoms may be due to irritable bowel syndrome, non-celiac gluten sensitivity, lactose intolerance, small intestinal bacterial overgrowth, or inflammatory bowel disease.

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Related Health Conditions

Celiac Disease

The primary condition anti-tTG detects — an autoimmune disorder where gluten triggers immune-mediated damage to the small intestine. Affects about 1% of the population but remains undiagnosed in most. A strict gluten-free diet allows the intestine to heal and prevents long-term complications. Learn more →

Iron Deficiency Anemia

Celiac disease is an important and often overlooked cause of iron deficiency anemia. The intestinal damage impairs iron absorption in the duodenum, where most dietary iron is absorbed. Patients with iron deficiency that doesn’t respond to supplementation should be tested for celiac disease — treating the underlying celiac improves iron absorption and resolves anemia. Learn more →

Osteoporosis

Celiac disease significantly increases osteoporosis risk due to malabsorption of calcium and vitamin D over years. Bone loss can be severe and occur at young ages when osteoporosis is unexpected. Screening for celiac is recommended in patients with unexplained osteoporosis, especially if other risk factors are absent. Gluten-free diet and nutritional supplementation improve bone density. Learn more →

Dermatitis Herpetiformis

Dermatitis herpetiformis is essentially “celiac disease of the skin” — an intensely itchy, blistering rash typically appearing on elbows, knees, and buttocks. Virtually all patients with dermatitis herpetiformis have intestinal changes of celiac disease, even if asymptomatic. Anti-tTG is usually positive. A gluten-free diet treats both the skin and intestinal manifestations. Learn more →

Type 1 Diabetes

Type 1 diabetes and celiac disease share genetic risk factors (HLA genes), and 3-10% of type 1 diabetics have celiac disease — far higher than the 1% general population prevalence. Guidelines recommend celiac screening at diabetes diagnosis and periodically thereafter. Managing both conditions requires attention to carbohydrate counting on a gluten-free diet. Learn more →

Autoimmune Thyroid Disease

Hashimoto’s thyroiditis and Graves’ disease are more common in celiac patients, and vice versa. This clustering of autoimmune conditions means that finding one should prompt consideration of testing for others. Patients with autoimmune thyroid disease who have GI symptoms, unexplained nutrient deficiencies, or other celiac-associated features should be screened. Learn more →

Infertility and Pregnancy Complications

Undiagnosed celiac disease is associated with infertility, recurrent miscarriage, intrauterine growth restriction, and low birth weight. Nutrient deficiencies and systemic inflammation may contribute. Testing for celiac disease is recommended in women with unexplained infertility or recurrent pregnancy loss — treatment with a gluten-free diet often improves fertility outcomes. Learn more →

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Related Biomarkers Often Tested Together

Total IgA — Essential to check alongside anti-tTG; IgA deficiency causes false-negative results.

Anti-Endomysial Antibodies (EMA) — Highly specific confirmatory test for celiac disease.

Deamidated Gliadin Peptide (DGP) — Useful in IgA deficiency and children under 2.

Iron Studies — Celiac commonly causes iron deficiency.

Vitamin D, B12, Folate — Often deficient in celiac due to malabsorption.

Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.