The Tissue Transglutaminase (TTG) IgA test is a standard screening tool used when celiac disease is suspected. TTG stands for tissue transglutaminase, which is a common enzyme found throughout the body, including the gut lining. This blood test measures the presence and quantity of autoantibodies produced by the immune system that mistakenly target this enzyme. Finding elevated levels of these autoantibodies is generally a strong indicator that further diagnostic investigation is necessary.
What is the TTG Autoantibody?
Tissue transglutaminase is an enzyme that helps repair damaged cells and tissues within the body. In individuals with celiac disease, the immune system reacts abnormally to gluten, a protein found in wheat, barley, and rye. This chronic immune reaction triggers the production of autoantibodies that attack the body’s own TTG enzyme.
The test specifically measures the Immunoglobulin A (IgA) class of these antibodies, which are the most relevant in the diagnosis of celiac disease. The production of these antibodies is a direct consequence of the immune system confusing the TTG enzyme with an altered form of the gluten protein.
Interpreting Elevated TTG Levels
The interpretation of TTG-IgA test results relies on comparing the measured value to a laboratory’s established reference range, often expressed in units per milliliter (U/mL). A result below the cutoff, typically less than 4.0 U/mL or 7.0 U/mL, is usually considered negative or normal. However, the exact thresholds vary between laboratories, so it is important to always refer to the specific ranges provided on the test report.
A borderline or weak positive result, which might fall between 4.0 and 10.0 U/mL, suggests a possibility of celiac disease but is not definitive. These indeterminate results often require repeat testing or additional serology tests to clarify the diagnosis. A result greater than 10.0 U/mL is generally considered a positive result, making a diagnosis of celiac disease likely.
A “high” TTG level is often defined as a value that is significantly elevated, sometimes more than ten times the upper limit of the normal range. For example, if the upper limit is 20 U/mL, a result over 200 U/mL would be considered highly elevated. Higher antibody levels correlate with a greater probability of having celiac disease, and in some cases, with more extensive damage to the small intestine lining.
Celiac Disease and High TTG
A high TTG-IgA result is a highly sensitive and specific marker for celiac disease, meaning it is an effective tool for identifying the condition. When people with genetic susceptibility to celiac disease consume gluten, the immune response targets the TTG enzyme in the small intestine. This sustained immune attack causes inflammation and damage to the villi, which are the small, finger-like projections responsible for nutrient absorption.
The presence of high TTG antibodies indicates this ongoing autoimmune process in the gut. In fact, a TTG-IgA level significantly elevated—more than ten times the upper limit of normal—is nearly 100% predictive of celiac disease in symptomatic individuals.
TTG antibodies can be elevated in rare instances not related to celiac disease, such as in certain liver diseases or other autoimmune conditions. However, a positive TTG-IgA test remains overwhelmingly linked to celiac disease, especially when combined with typical symptoms.
Required Next Steps After a High Result
Receiving a high TTG-IgA result is an indication for further diagnostic investigation, not an immediate confirmation of celiac disease. It is absolutely necessary to continue consuming a gluten-containing diet until all diagnostic testing is completed. Stopping gluten consumption prematurely can heal the intestinal damage and lower antibody levels, which may interfere with the accuracy of confirmatory tests.
The next step generally involves a referral to a gastroenterologist, a specialist in digestive disorders. The specialist will often order additional tests:
- Additional blood tests, such as the IgA Endomysial Antibody (EMA) or Deamidated Gliadin Peptide (DGP) tests, to further confirm the diagnosis.
- An upper endoscopy with a small intestinal biopsy, which is the gold standard for confirmation. This procedure allows the physician to visually inspect the small intestine and take tissue samples to check for characteristic villous atrophy.
- Genetic testing for HLA-DQ2 and HLA-DQ8, which can be used as a supportive tool. A negative genetic test effectively rules out celiac disease, but a positive result only indicates a genetic predisposition.