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Tissue Transglutaminase IgA Antibody (tTG-IgA)


Definition


  • Celiac disease (CD) is an immune-mediated enteropathy caused by a permanent sensitivity to gluten in genetically susceptible individuals. Testing should begin with serologic evaluation, and the most sensitive and specific tests are tissue transglutaminase IgA antibody (tTG-IgA) and endomysial IgA antibody (EMA-IgA), which have equivalent diagnostic accuracy. Anti-tTG antibodies are highly sensitive and specific for the diagnosis of CD. The enzyme tTG is the major target antigen recognized by anti-endomysial antibodies. Based on the current evidence and practical considerations, including accuracy, reliability, and cost, measurement of tTG-IgA is recommended for initial testing for CD. Although as accurate as tTG, measurement of IEMA-IgA is observer dependent and, therefore, more subject to interpretation error and added cost. Because of the inferior accuracy of the antigliadin antibody (AGA) tests, the use of AGA IgA and AGA IgG tests is no longer recommended for detecting CD.
  • Normal range: <20 U (negative).

Use


  • Diagnosis of certain gluten-sensitive enteropathies, such as CD and dermatitis herpetiformis
  • Monitoring adherence to gluten-free diet in patients with dermatitis herpetiformis and CD
  • Evaluating children with failure to thrive

Interpretation


Increased In


  • CD (20 " “30 U: weak positive; >30 U: moderate to strong positive)
  • Autoimmune skin disease and dermatitis herpetiformis

Limitations


  • All testing should be performed while patients are on a gluten-containing diet.
  • IgA deficiency is more common in CD (2 " “5%) than in the general population (<0.5%). The EMA-IgA and tTG-IgA serology tests will be falsely negative in untreated CD in patients with IgA deficiency. As a result, total serum IgA can be measured in addition to EMA-Ig A or tTG-IgA, especially when there is heightened clinical suspicion for CD and IgA markers are negative. If total IgA levels are abnormally low, an IgG-based assay should be used to test for CD.
  • The IgG antigliadin assay has been traditionally used in this circumstance but is not ideal, since it yields frequent false-positive results. Therefore, serum IgG-tTG or IgG deamidated gliadin peptide (DPG) tests are preferable. Negative results on testing for HLA DQ2 or DQ8 can also help exclude the diagnosis in this setting.
  • If serology is negative and/or there is substantial clinical doubt remaining, then further investigation should be performed with endoscopy and bowel biopsy. This is especially important in patients with frank malabsorptive symptoms, since many syndromes can mimic CD. For the patient with frank malabsorptive symptoms, bowel biopsy should be performed regardless of serologic test results.
  • False-positive tests are rare but have been reported in patients with other autoimmune syndromes. Because the tTG antigen is derived from liver cells, false-positive results may be seen in patients with autoimmune liver disease.

Suggested Reading


1Hill ‚  ID, Dirks ‚  MH, Liptak ‚  GS Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr.  2005;40(1):1 " “19.
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