Tissue transglutaminase (TTG) is an enzyme naturally present in the body. An elevated TTG level in a blood test suggests an immune response has occurred. Understanding this result is important for determining the cause and next steps. This article explains what TTG is, what an elevated level signifies, and recommended actions.
Understanding Tissue Transglutaminase (TTG)
Tissue transglutaminase (TTG), also known as transglutaminase 2, is a calcium-dependent enzyme found throughout the body in various cellular compartments. It primarily functions in protein cross-linking, forming stable bonds within or between proteins. This enzymatic activity contributes to bodily functions such as tissue repair, wound healing, stabilizing the extracellular matrix, and promoting cell adhesion.
A blood test for TTG measures antibodies the immune system produces against the enzyme, not the enzyme itself. When the immune system mistakenly targets TTG, it generates specific antibodies. These anti-TTG antibodies, particularly IgA antibodies, are commonly measured as a marker for certain conditions where an autoimmune response is suspected.
Interpreting an Elevated TTG Level
An elevated level of tissue transglutaminase antibodies most commonly indicates the presence of celiac disease. Celiac disease is an autoimmune condition where ingesting gluten, a protein found in wheat, barley, and rye, triggers an immune system attack on the small intestine. In this process, TTG deamidates gliadin peptides from gluten, which increases their binding to specific human leukocyte antigen (HLA) molecules (HLA-DQ2 and HLA-DQ8) on immune cells, thereby initiating an immune response.
Immunoglobulin A (IgA) anti-TTG antibodies are considered the primary diagnostic marker for celiac disease due to their high sensitivity and specificity. An elevated result for IgA TTG signifies that the antibody level in the blood is above a certain threshold, suggesting an active immune reaction. However, in some individuals with an IgA deficiency, the IgA TTG test may yield a false-negative result because their bodies do not produce sufficient IgA antibodies. In such cases, immunoglobulin G (IgG) anti-TTG antibodies may be measured instead to aid in diagnosis.
Other Reasons for High TTG
While celiac disease is the most frequent cause, elevated TTG antibody levels can also be observed in other contexts. Other autoimmune conditions, such as Type 1 diabetes, autoimmune thyroid diseases (like Hashimoto’s thyroiditis or Graves’ disease), and rheumatoid arthritis, have been associated with increased TTG antibodies. Autoimmune liver diseases, including autoimmune hepatitis, may also lead to elevated levels.
Furthermore, inflammatory bowel diseases and certain infections can sometimes result in a transient rise in TTG antibodies. Chronic liver disease, especially when accompanied by elevated total IgA levels, can also be a factor. These other causes are generally less common for significant TTG elevation, and a healthcare professional will consider all aspects of a patient’s health history and symptoms to determine the underlying reason for the elevated levels.
What to Do After a High TTG Result
Receiving a high TTG result warrants a consultation with a healthcare professional, such as a gastroenterologist, for further evaluation and diagnosis. An elevated TTG level is typically a screening indicator, and additional diagnostic tests are often necessary to confirm a condition like celiac disease. These confirmatory steps frequently include a small intestinal biopsy, which allows for the direct assessment of mucosal damage and villous atrophy, characteristic features of celiac disease.
Genetic testing for HLA-DQ2 and HLA-DQ8 can also be performed, which helps to rule out celiac disease if these genes are absent, though their presence does not confirm the condition. Individuals should not begin a gluten-free diet before these diagnostic tests are completed. Eliminating gluten prematurely can cause antibody levels to decrease and intestinal healing to begin, potentially leading to inaccurate or false-negative test results and complicating the diagnostic process.