Tissue Transglutaminase (tTG), IgA

The Tissue Transglutaminase (tTG), IgA antibody test—also known as anti‑tTG IgA or transglutaminase antibodies, IgA—assists in the diagnosis of celiac disease and dermatitis herpetiformis and helps determine who should proceed to endoscopic small-bowel evaluation. It is also applied for targeted screening in high‑risk groups such as those with a family history of celiac disease, type 1 diabetes, or Down syndrome. Longitudinal measurement supports monitoring of response to a gluten‑free diet by tracking the decline in antibody concentrations over time.

Tissue transglutaminase catalyzes cross‑linking reactions between glutamine‑ and lysine‑rich proteins and is present in multiple tissues, including the intestinal submucosa. Ingested gluten provides gliadin peptides that are deamidated by tTG, which increases their immunogenicity. In genetically susceptible individuals this process drives an autoimmune response that injures small‑intestinal mucosa, producing villous atrophy and malabsorption. Serologic testing with tTG IgA demonstrates high diagnostic accuracy for celiac disease, with sensitivity approximately 81%–100% and specificity approximately 97%–99%, and helps identify candidates for endoscopic small‑bowel biopsy. Because selective IgA deficiency is more common among patients with celiac disease, measurement of total IgA and use of IgG‑based assays (eg, tTG IgG) are recommended when IgA deficiency is present. With strict gluten avoidance, tTG IgA concentrations generally decline over 6–12 months, allowing objective assessment of adherence to a gluten‑free diet. Celiac disease can be minimally symptomatic; therefore, periodic serologic screening is considered in risk groups, including first‑degree relatives and individuals with type 1 diabetes, autoimmune thyroiditis, or Down syndrome.