The Tissue Transglutaminase Immunoglobulin A (TTG IgA) test is a common blood screening tool used to evaluate individuals for Celiac Disease. Understanding the components measured and the context of the result is necessary for accurate interpretation. A normal result suggests a low likelihood of active Celiac Disease, but the diagnosis is complex and depends on multiple factors beyond a single number.
The Role of the TTG IgA Test
The TTG IgA test measures specific antibodies produced by the immune system in response to gluten consumption in genetically susceptible individuals. This is an indirect sign of the autoimmune response triggered by gluten, not a measure of gluten itself. The target of this immune reaction is tissue transglutaminase (TTG), an enzyme naturally present throughout the body, including the small intestine.
TTG modifies gluten peptides after they enter the intestinal lining. It acts as a deamidating enzyme, altering the structure of the gluten protein gliadin and making it more likely to provoke an immune response. In Celiac Disease, the body mistakenly identifies TTG as foreign and produces IgA-class autoantibodies against it. The presence of these specific autoantibodies in the bloodstream is what the TTG IgA test detects, making it a highly sensitive first-line screening tool.
Interpreting TTG IgA Levels
A “normal” TTG IgA result indicates a low amount of autoantibodies, suggesting Celiac Disease activity is not present. While reference ranges vary between laboratories, a result below 20 Units per milliliter (U/mL) is often cited as the common threshold for a negative result. A negative result means the likelihood of having active Celiac Disease is low, particularly if the patient was consuming gluten regularly before the test.
Results in a borderline or indeterminate range (sometimes between 20 U/mL and 30 U/mL) are inconclusive and may prompt repeat testing or the use of a secondary serology test. A strongly positive result, such as one over 30 U/mL or greater than ten times the upper limit of the normal range, is highly suggestive of active Celiac Disease. The level of elevation often correlates with the degree of damage in the small intestine. Extremely high antibody titers have a strong predictive value and indicate the need for further diagnostic steps.
Factors That Influence Test Accuracy
The reliability of the TTG IgA test depends on two major factors that can lead to an inaccurate negative result. One factor is IgA deficiency, a condition where the body produces insufficient Immunoglobulin A. Since the test specifically measures IgA antibodies, this deficiency can result in a false negative even if Celiac Disease is active. Because IgA deficiency is estimated to be ten to twenty times more common in people with Celiac Disease, guidelines recommend testing for total serum IgA alongside the TTG IgA test to rule out this possibility.
If total IgA deficiency is confirmed, testing shifts to an Immunoglobulin G (IgG) based antibody panel, such as the Deamidated Gliadin Peptide IgG (DGP IgG) or TTG IgG tests. The second factor is the patient’s diet leading up to the blood draw. Serological testing requires the patient to be consuming gluten regularly for the immune response to be active and antibodies to be produced. If a person has already started a gluten-free diet, the intestinal lining may heal, causing antibody levels to drop and leading to a misleadingly low or negative result. For an accurate diagnosis, a “gluten challenge” (consuming a specific amount of gluten daily for several weeks) is often necessary if the patient has been avoiding it.
Next Steps Following a Positive Result
A positive or highly elevated TTG IgA test result is a strong indicator of Celiac Disease but does not provide a definitive diagnosis on its own. Following this result, the next step involves a referral to a gastroenterologist for an upper endoscopy. During this procedure, a flexible tube is passed into the small intestine to visually inspect the intestinal lining.
The physician will take small tissue samples (a biopsy) from the duodenum. These samples are analyzed under a microscope to look for the characteristic intestinal damage of Celiac Disease, specifically the flattening of the villi. This histological evidence of villous atrophy is the accepted gold standard for confirming the diagnosis in adults. Once Celiac Disease is confirmed, management involves strict, lifelong adherence to a gluten-free diet to allow the intestinal lining to heal and prevent complications.