The acronym tTG stands for Tissue Transglutaminase, an enzyme naturally found within the body. In a medical context, particularly when testing for Celiac Disease, the term refers to the anti-tTG antibody blood test. This serological examination measures the concentration of antibodies the immune system produces against this specific enzyme. The presence of these antibodies serves as the most widely used initial screening tool for Celiac Disease in adults and older children. This central role in diagnosis stems directly from the complex biological reactions that occur when a person with Celiac Disease consumes gluten.
Tissue Transglutaminase: The Enzyme’s Normal Function
Tissue transglutaminase (TG2) is a calcium-dependent enzyme that plays a broad role in cellular maintenance and repair throughout the body. Its primary function is to catalyze transamidation, a process that forms stable, covalent bonds between proteins. This cross-linking ability acts as a molecular “glue” to link protein chains together, contributing to the structural integrity of tissues.
This enzyme is particularly active in stabilizing the extracellular matrix, the network that surrounds and supports cells. For instance, tTG is involved in wound healing and tissue damage repair. When cells are injured, tTG is released, promoting quick stabilization of the damaged area and fortifying the surrounding tissue structure.
The enzyme also performs deamidation, converting the amino acid glutamine into glutamic acid. This modification changes the electrical charge of the protein, affecting how it interacts with other molecules. While tTG primarily performs cross-linking under normal conditions, the environment of the inflamed small intestine favors the deamidation reaction.
The Autoimmune Role in Celiac Disease
The transition of tTG to a central figure in Celiac Disease pathology begins when a genetically susceptible individual ingests gluten, specifically the gliadin components. Gliadin peptides are rich in glutamine, making them excellent substrates for the tTG enzyme. When these gliadin peptides reach the small intestine, they encounter tTG released into the surrounding tissue due to mucosal damage or inflammation.
The enzyme acts as a deamidase, chemically altering the gliadin peptides by converting glutamine residues into glutamic acid residues. This process introduces a negative charge to the gliadin protein segment, which has profound immunological consequences.
The newly modified, deamidated gliadin fits precisely into the binding groove of the HLA-DQ2 or HLA-DQ8 molecules found on immune cells in the gut. This presentation of the deamidated gliadin to the immune system’s T-cells triggers a robust and inappropriate immune response. Activated T-cells drive the inflammatory reaction that causes characteristic damage to the lining of the small intestine.
The immune system begins to recognize not only the modified gliadin but also the tTG enzyme itself as a foreign threat. The body produces antibodies, known as anti-tTG antibodies, that target its own tissue transglutaminase enzyme. This production of autoantibodies against tTG is a defining feature of Celiac Disease, leading to chronic inflammation and damage to the villi of the small intestine. The resulting damage leads to nutrient malabsorption.
Interpreting the tTG Antibody Test
The tTG antibody test uses a blood sample to measure the level of anti-tTG antibodies, typically focusing on the Immunoglobulin A (IgA) class. The tTG-IgA test is the recommended first-line screening tool due to its high sensitivity and specificity in detecting Celiac Disease. A positive result, usually defined by a titer exceeding a laboratory-specific cutoff value, strongly suggests the presence of the condition.
Test results are often reported in units per milliliter (U/mL) and may be categorized as negative, weak positive, or strongly positive. Levels that are significantly elevated, sometimes ten times the upper limit of normal, have a nearly 100% positive predictive value for Celiac Disease in symptomatic individuals. However, no single blood test can provide a definitive diagnosis, and a small intestinal biopsy via endoscopy is generally required to confirm the characteristic tissue damage.
A necessary consideration when ordering the test is the potential for IgA deficiency. Since IgA deficiency is more common in individuals with Celiac Disease, a total serum IgA measurement is often included in the initial blood work. If a patient is found to be IgA deficient, the tTG-IgA test will produce a false negative result, regardless of whether Celiac Disease is present.
In cases of IgA deficiency, a different test, such as the tTG-IgG or the Deamidated Gliadin Peptide (DGP) IgG antibody test, is used instead. For all serological testing to be accurate, the patient must be consuming a gluten-containing diet for a period before the blood draw. Testing while on a gluten-free diet can cause the antibody levels to drop, leading to a misleadingly negative result.