Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO, and Schuppan D. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 3: 797-801

Department of Gastroenterology, Klinikum Benjamin Franklin, Free University of Berlin, Germany.
Nature Medicine (Impact Factor: 27.36). 08/1997; 3(7):797-801. DOI: 10.1038/nm0797-797
Source: PubMed


Celiac disease is characterized by small intestinal damage with loss of absorptive villi and hyperplasia of the crypts, typically leading to malabsorption. In addition to nutrient deficiencies, prolonged celiac disease is associated with an increased risk for malignancy, especially intestinal T-cell lymphoma. Celiac disease is precipitated by ingestion of the protein gliadin, a component of wheat gluten, and usually resolves on its withdrawal. Gliadin initiates mucosal damage which involves an immunological process in individuals with a genetic predisposition. However, the mechanism responsible for the small intestinal damage characteristic of celiac disease is still under debate. Small intestinal biopsy with the demonstration of a flat mucosa which is reversed on a gluten-free diet is considered the main approach for diagnosis of classical celiac disease. In addition, IgA antibodies against gliadin and endomysium, a structure of the smooth muscle connective tissue, are valuable tools for the detection of patients with celiac disease and for therapy control. Incidence rates of childhood celiac disease range from 1:300 in Western Ireland to 1:4700 in other European countries, and subclinical cases detected by serological screening revealed prevalences of 3.3 and 4 per 1000 in Italy and the USA, respectively. IgA antibodies to endomysium are particularly specific indicators of celiac disease, suggesting that this structure contains one or more target autoantigens that play a role in the pathogenesis of the disease. However, the identification of the endomysial autoantigen(s) has remained elusive. We identified tissue transglutaminase as the unknown endomysial autoantigen. Interestingly, gliadin is a preferred substrate for this enzyme, giving rise to novel antigenic epitopes.

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Available from: Detlef Schuppan, Oct 08, 2014
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    • "The prevalence of CD in Europe and North America ranges from 1:80 to 1:300 [11] [12] [28] [29] [32] [61] [66]. In the pathogenesis of CD, ap i v o t a lc o n t r i b u t i o ni sm a d eb ya dysregulated immune response directed against tissue transglutaminase type 2 (TG2) which has been identified as a prominent autoantigen of CD [27]. The exogenous trigger of this dysregulated immune response is gluten which is ingested along with grain-containing food. "
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    • "Celiac disease (CD) is an immune-mediated condition that leads to inflammation of the small intestinal mucosa resulting in damage, loss of absorptive villi and ultimately nutrient malabsorption [85]. CD is triggered by gliadin, a protein found in wheat gluten, and other alcohol-soluble proteins (prolamines) contained in barley and rye [86]. "
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    • "One of the most common diseases with autoimmune features that suffers from a lack of animal models is celiac disease (CD). CD is characterized by the presence of specific antibodies recognizing an endomysial autoantigen identified as type 2 transglutaminase (TG2) [25]. The antibody level against TG2 increases upon exposure to gluten, and decreases during the course of a gluten-free diet [26]. "
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