What do positive tissue transglutaminase (tTG) Immunoglobulin G (IgG) and Immunoglobulin A (IgA) antibodies indicate?

From the Guidelines

Positive tissue transglutaminase (tTG) Immunoglobulin G (IgG) and Immunoglobulin A (IgA) antibodies are highly indicative of celiac disease, with the IgA tTG test being the most sensitive and specific serological marker for this condition. The presence of these antibodies suggests an autoimmune response to gluten, where the body mistakenly targets the tTG enzyme that modifies gluten peptides in the intestine 1.

Key Points to Consider

• The IgG tTG test is particularly useful for diagnosing celiac disease in patients with IgA deficiency, which affects approximately 2-3% of celiac patients 1.
• While positive antibodies strongly suggest celiac disease, definitive diagnosis typically requires intestinal biopsy confirmation, although recent guidelines suggest moving towards biopsy-avoidance strategies in certain cases 1.
• These antibodies develop in response to gluten exposure, and patients with positive results should maintain a regular gluten-containing diet until diagnostic workup is complete, as eliminating gluten prematurely can affect test accuracy 1.
• Screening for celiac disease is recommended in certain high-risk populations, such as those with type 1 diabetes, with guidelines suggesting screening soon after diabetes diagnosis and then again after 5 years 1.

Implications for Diagnosis and Treatment

• The presence of positive tTG IgG and IgA antibodies is a strong indicator of celiac disease, and patients with these results should be referred for further diagnostic workup and consideration of a gluten-free diet.
• A gluten-free diet is the only treatment for celiac disease, and it is essential for preventing complications such as osteoporosis, iron deficiency, and growth failure 1.
• Consultation with a registered dietitian nutritionist experienced in managing both diabetes and celiac disease is recommended for individuals with confirmed celiac disease 1.

From the Research

Tissue Transglutaminase IgG and IgA Antibodies

• Tissue transglutaminase (tTG) IgA antibodies are a hallmark for celiac disease (CD) 2, 3, 4
• IgA and IgG antibodies to tTG are significantly higher in serum of untreated patients with celiac disease versus those in the control group 4
• The presence of IgA anti-tTG2 antibody is a relevant marker in celiac disease, and its levels correlate inversely with the duration of gluten-free diet (GFD) 5

Diagnostic Indications

• Positive tTG IgA antibodies indicate celiac disease, and their levels decrease with the adoption of a gluten-free diet 2, 3, 4, 5
• IgG antibodies to tTG also have diagnostic value, although IgA antibodies are more specific for celiac disease 4
• The sensitivity, specificity, and positive predictive value of IgA and IgG antitissue tTG are 92% and 21%, 98% and 97%, and 98% and 83%, respectively 4

Clinical Implications

• The detection of tTG IgA and IgG antibodies can be used to monitor the response to gluten-free diet in patients with celiac disease 2, 5
• The persistence of positive antibody levels in some patients, even after several years of gluten-free diet, may indicate suboptimal treatment response or ongoing intestinal damage 2, 5
• The role of tTG antibodies in the immunopathology of celiac disease is still a matter of debate, but they are thought to contribute to the development of the typical celiac lesion 3, 6