The tissue transglutaminase IgA (tTG-IgA) test is a blood screening tool for celiac disease. It measures the level of IgA antibodies targeting the enzyme tissue transglutaminase. A positive result indicates the patient’s immune system is mistakenly attacking its own tissues, a hallmark of this autoimmune disorder. This non-invasive serology test is the most sensitive and specific first-line screening option for most individuals older than two years of age.
The Enzyme: Tissue Transglutaminase
Tissue transglutaminase (tTG) is an enzyme found throughout the body, including the lining of the gut. Its normal function is to catalyze a biochemical reaction that cross-links proteins, forming strong bonds necessary for tissue maintenance and repair. When tissue damage occurs, such as in the small intestine, tTG is released from cells to help mend the injury.
tTG is a calcium-dependent enzyme. Beyond cross-linking, it possesses deamidation activity, which is the chemical modification of certain amino acids within a protein. While deamidation is a normal function, it becomes a central component in the development of celiac disease, setting the stage for the body’s mistaken immune response.
The Autoimmune Response in Celiac Disease
The production of tTG-IgA antibodies results from an interaction between genetics, gluten protein, and the tTG enzyme. The process begins when gluten enters the small intestine and breaks down into peptides, including gliadin. In genetically susceptible individuals (those with HLA-DQ2 or HLA-DQ8 genes), the immune system is primed to react.
The tTG enzyme performs its deamidation function on the gliadin peptides, converting glutamine into glutamic acid. This modification gives the gliadin a negative electrical charge, increasing its affinity for HLA-DQ2 and HLA-DQ8 molecules on immune cells. This enhanced binding allows immune cells to present the modified gliadin to T-cells, triggering an immune response.
The immune system then mistakenly identifies the tTG enzyme itself—which is often bound near the deamidated gliadin—as a threat. It begins producing IgA-class autoantibodies that target the body’s own tTG enzyme. These anti-tTG antibodies circulate in the blood, serving as a reliable marker of the ongoing autoimmune attack that characterizes celiac disease.
Interpreting tTG-IgA Test Results
The tTG-IgA test is performed via a simple blood draw, and results are reported numerically compared to the laboratory’s upper limit of normal. A negative result indicates a low probability of celiac disease, while an elevated antibody level strongly suggests the condition.
A critical consideration is the necessity of a sustained gluten-containing diet at the time of testing. If a person has started a gluten-free diet, tTG-IgA antibody levels can decrease, leading to a false-negative result. For accuracy, the patient must consume the equivalent of at least one to two slices of bread daily for several weeks prior to the blood draw. Patients should not remove gluten from their diet before all diagnostic testing is complete.
IgA Deficiency
IgA deficiency is a significant limitation, as it is more common in people with celiac disease. Since the tTG-IgA test relies on the body producing IgA antibodies, an IgA deficient person will not produce them, resulting in a false negative. Therefore, the total serum IgA level is usually measured alongside the tTG-IgA test to rule out this deficiency. If IgA deficiency is confirmed, alternative antibody tests, such as the deamidated gliadin peptide IgG or tTG IgG, must be used for screening.
Clinical Follow-Up and Management
A positive tTG-IgA blood test is a strong initial screening result, but it is usually not sufficient for a definitive diagnosis of celiac disease. Following a positive test, the patient is referred to a gastroenterologist for confirmation. The standard method is an upper endoscopy with a small intestinal biopsy.
During the endoscopy, the doctor takes tissue samples from the small intestine. These samples are examined for villous atrophy—the flattening and damage to the finger-like projections called villi—which confirms the intestinal damage characteristic of the disease. Some medical guidelines allow for diagnosis without a biopsy in specific cases, particularly in children with tTG-IgA levels more than ten times the upper limit of normal.
Once celiac disease is confirmed, management requires strict, lifelong adherence to a gluten-free diet. This involves avoiding foods containing wheat, rye, and barley. The diet is the only treatment that allows the damaged intestinal lining to heal, resolving symptoms and restoring normal nutrient absorption. Monitoring often involves repeating the tTG-IgA test, as antibody levels should decrease and normalize once gluten is successfully removed.