What is the significance of Tissue Transglutaminase (TTG) Immunoglobulin A (IgA)?

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From the Guidelines

TTG IgA is a highly sensitive and specific blood test for screening celiac disease, with values above 20 U/mL indicating a strong likelihood of the condition, as supported by the most recent study from 2022 1. The test measures antibodies produced against the enzyme tissue transglutaminase when a person with celiac disease consumes gluten.

  • A positive TTG IgA test result suggests celiac disease, with sensitivity and specificity exceeding 95% in most populations, according to the study published in Alimentary Pharmacology and Therapeutics 1.
  • However, confirmation typically requires an intestinal biopsy while the patient is still consuming gluten.
  • The test may yield false negatives in IgA-deficient individuals, affecting about 2-3% of celiac patients, so total IgA levels are often measured simultaneously, as recommended by the American College of Gastroenterology 1.
  • For accurate results, patients should continue consuming gluten-containing foods before testing, as eliminating gluten can normalize antibody levels and lead to false negatives.
  • TTG IgA testing is recommended for individuals with symptoms suggestive of celiac disease, those with first-degree relatives who have celiac disease, or patients with associated conditions like type 1 diabetes or autoimmune thyroid disease, as stated in the study from 2022 1. Some key points to consider when interpreting TTG IgA results include:
  • The threshold for a positive test result may vary by laboratory, but values above 20 U/mL are generally considered indicative of celiac disease, as seen in the hypothetical adult and pediatric cohorts 1.
  • The test is highly accurate, but false negatives can occur in IgA-deficient individuals, emphasizing the importance of measuring total IgA levels simultaneously, as shown in the study's results table 1.
  • A gluten-free diet can normalize antibody levels, leading to false negatives, so patients should continue consuming gluten-containing foods before testing, as highlighted in the 2022 study 1.

From the Research

Significance of Tissue Transglutaminase (TTG) Immunoglobulin A (IgA)

  • Tissue Transglutaminase (TTG) Immunoglobulin A (IgA) is a significant marker in the diagnosis and monitoring of celiac disease 2, 3, 4, 5, 6
  • The presence of IgA TTG antibodies is an indicator of an immune response to gluten, and their levels can decrease with adherence to a gluten-free diet 2, 4, 6
  • IgA TTG antibodies have high sensitivity and specificity for diagnosing celiac disease, making them a useful tool for initial testing 2, 5, 6
  • However, a normal TTG level does not necessarily predict recovery of villous atrophy in patients with celiac disease on a gluten-free diet 5
  • IgA TTG antibodies can also be used to monitor compliance with a gluten-free diet, as their levels correlate with the duration of gluten exposure 3, 4, 6

Clinical Applications

  • IgA TTG antibodies are useful in the initial diagnosis of celiac disease, particularly in patients with symptoms suggestive of the condition 2, 5, 6
  • They can also be used to monitor the effectiveness of a gluten-free diet and to detect potential gluten exposure 3, 4, 6
  • However, it is essential to consider the possibility of IgA deficiency in patients with celiac disease, as this can lead to false-negative results 2

Limitations

  • IgA TTG antibodies are not perfect markers, and their levels can be influenced by various factors, such as the duration of gluten exposure and the presence of other autoimmune disorders 3, 5
  • A positive IgA TTG result should be confirmed with a small bowel biopsy to establish a definitive diagnosis of celiac disease 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Celiac disease.

American family physician, 2007

Research

[Anti-transglutaminase antibody in adults with celiac disease and their relation to the presence and duration of gluten-free diet].

Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru, 2018

Research

What is the role of serologic testing in celiac disease? A prospective, biopsy-confirmed study with economic analysis.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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