The anti-Tissue Transglutaminase (Anti-tTG) IgA test is the primary blood screening method used to identify individuals who may have Celiac Disease. This test measures the level of specific autoantibodies the body produces when the immune system reacts abnormally to gluten. A positive result indicates the body is generating an immune response against its own enzyme, a hallmark of the condition. Determining the normal range for this antibody level is a crucial first step in evaluating a person suspected of having an autoimmune reaction to gluten.
What Does Tissue Transglutaminase Do?
Tissue transglutaminase (tTG), specifically the Type 2 enzyme, is a calcium-dependent protein found throughout the body, but it is particularly relevant to the small intestine. Its natural function involves catalyzing the post-translational modification of proteins, primarily through cross-linking to help repair cellular damage and maintain tissue structure. It also performs a chemical reaction called deamidation.
In individuals genetically predisposed to Celiac Disease, this deamidation process initiates the autoimmune cascade. When gluten, a protein complex found in wheat, barley, and rye, reaches the small intestine, the tTG enzyme alters its structure. It chemically converts glutamine residues in the gluten fragments (gliadin) into negatively charged glutamic acid residues.
These newly deamidated gluten peptides fit perfectly into specific human leukocyte antigen (HLA) molecules, such as HLA-DQ2 or HLA-DQ8, on immune cells. The immune system mistakenly views these altered peptides as a foreign invader, launching an aggressive response. As a result, the body begins producing autoantibodies that target the tTG enzyme itself, which is what the blood test measures. The presence of these anti-tTG antibodies is a direct sign that the immune system is actively attacking the self-protein in the intestinal lining.
Interpreting Anti-tTG Numerical Results
The level of anti-tTG antibodies in the blood is reported in units per milliliter (U/mL) or sometimes as a relative index. The definition of a “normal” or negative result can vary between different laboratories and testing kits. Generally, a normal or negative result means Celiac Disease is unlikely and typically falls below a specific cutoff, such as less than \(4.0 \text{ U/mL}\) or \(<20 \text{ U/mL}[/latex], depending on the assay. A result in this range suggests that the immune system is not producing a measurable antibody response to the tTG enzyme. Results that fall into a borderline or indeterminate range, often between [latex]4.0[/latex] to [latex]10.0 \text{ U/mL}[/latex] or [latex]20[/latex] to [latex]30 \text{ U/mL}[/latex], require careful interpretation and often follow-up testing. These weak positive results may suggest a very early stage of the disease, a minor inflammatory condition other than Celiac Disease, or could simply be an artifact of the testing process. Clinicians typically recommend repeating the test or pursuing additional serological markers in such cases. A positive result, usually defined as greater than [latex]10.0 \text{ U/mL}[/latex] or [latex]>30 \text{ U/mL}\), strongly suggests the presence of Celiac Disease, especially if the patient is consuming gluten. A very high titer, often defined as being 10 times the upper limit of normal (ULN) for the specific lab assay, is considered highly predictive of the condition. For example, if the ULN is \(10 \text{ U/mL}\), a result of \(100 \text{ U/mL}\) or higher carries a very high probability of Celiac Disease.
It is important that the anti-tTG IgA test is always accompanied by a measurement of total serum IgA. Immunoglobulin A (IgA) is the specific class of antibody being measured, and a significant portion of people with Celiac Disease also have IgA deficiency. If a patient is IgA deficient, the anti-tTG IgA test will falsely appear negative even if Celiac Disease is present, because the body cannot produce enough of the IgA class antibodies to be measured. In such cases, the diagnosis must rely on an IgG-based test, such as the deamidated gliadin peptide (DGP) IgG or anti-tTG IgG antibody tests.
Diagnosis and Follow-Up After High Levels
A confirmed high anti-tTG antibody level is a strong indicator of Celiac Disease, but it does not constitute a definitive diagnosis on its own. The next necessary step following a positive blood test is a referral for an upper endoscopy with a small intestinal biopsy. This procedure is performed while the patient is still consuming gluten and allows a gastroenterologist to visually inspect the small intestine and collect tissue samples.
The biopsy is necessary to confirm the diagnosis by assessing the degree of damage to the intestinal lining, specifically looking for villous atrophy, which is the flattening of the small, finger-like projections called villi. This histological confirmation is generally considered the standard for diagnosing Celiac Disease in adults. A biopsy may sometimes be avoided in children who have very high antibody titers and other supporting evidence.
The treatment for confirmed Celiac Disease is a strict, lifelong adherence to a gluten-free diet (GFD). The complete elimination of gluten from the diet stops the immune reaction, allowing the small intestine to heal and the villi to recover their normal structure and function. Nutritional counseling with a dietitian specializing in Celiac Disease is important to ensure the patient understands how to avoid cross-contamination and maintain a nutritionally complete diet.
Follow-up blood tests to monitor anti-tTG levels are routinely conducted to track the patient’s recovery and adherence to the GFD. As the intestinal lining heals and the immune response subsides, the antibody levels are expected to decrease significantly. While a substantial drop should be seen within a few months, it can take six months to over a year for the anti-tTG levels to fully normalize. Persistently elevated antibody levels suggest that the patient may be inadvertently consuming gluten or that the body is experiencing another complication, prompting a review of the diet and further medical investigation.