What are the implications of elevated tissue transglutaminase (tTG) Immunoglobulin A (IgA) levels?

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Last updated: April 23, 2025View editorial policy

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From the Guidelines

Tissue transglutaminase IgA (tTG-IgA) is the preferred initial screening test for celiac disease, with a high sensitivity of 90.7% in adults and 97.7% in children, as reported in a 2022 systematic review with meta-analysis 1.

Key Points to Consider

  • The test measures antibodies against the enzyme tissue transglutaminase, which are produced when gluten triggers an immune response in people with celiac disease.
  • A positive tTG-IgA result strongly suggests celiac disease but requires confirmation with an intestinal biopsy for definitive diagnosis.
  • Total IgA levels should be measured simultaneously to avoid false-negative results in cases of IgA deficiency, which occurs in about 2-3% of celiac patients.
  • In cases of IgA deficiency, alternative tests like deamidated gliadin peptide (DGP) IgG or tTG-IgG should be used.
  • For accurate results, patients should continue consuming gluten (equivalent to at least 2 slices of bread daily) for 6-8 weeks before testing, as a gluten-free diet can normalize antibody levels and lead to false-negative results.

Clinical Application

The American Diabetes Association recommends screening for celiac disease in patients with type 1 diabetes using tTG antibodies or EMA, with documentation of normal serum IgA levels 1. The AGA Institute also supports the use of IgA tTGA as the most efficient single serologic test for the detection of celiac disease in the primary care setting 1.

Important Considerations

  • The sensitivity and specificity of IgA tTG may vary depending on the population being tested, with higher sensitivity in children (97.7%) compared to adults (90.7%) 1.
  • The test is particularly useful for monitoring dietary compliance in diagnosed celiac patients, with decreasing antibody levels indicating successful gluten avoidance.

From the Research

Tissue Transglutaminase IgA

  • Tissue transglutaminase (tTG) IgA antibodies are a hallmark for celiac disease (CD) 2, 3
  • In CD patients on gluten-free diet (GFD), these antibodies are transient and their normalization depends on the assay used 2
  • The sensitivity and specificity of IgA and IgG tissue-transglutaminase antibodies assay are high, making them useful for diagnosis and monitoring of CD 4
  • Strongly positive tissue transglutaminase antibodies are associated with Marsh 3 histopathology in adult and pediatric celiac disease 5
  • Autoantibodies against tTG play a role in the immunopathology of the celiac mucosal lesion, inhibiting intestinal epithelial cell differentiation and inducing intestinal epithelial cell proliferation 6

Assay Characteristics

  • Different tTG-IgA assays have varying characteristics, with chemiluminescence immuno-assays (CLIA) being more sensitive than fluorochrome-enzyme immuno-assay (FEIA) in detecting suboptimal treatment response in CD 2
  • The use of different assays can lead to discrepant results in patients on GFD, highlighting the need for careful selection of assays for monitoring response to treatment 2

Clinical Implications

  • High serologic IgA tissue transglutaminase antibodies (>or= 100 units) are highly specific for CD histopathology in pediatric patients and may be sufficient for diagnosis 5
  • The decline pattern of antibodies after gluten-free diet can be used to monitor compliance and treatment response 4

References

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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