IDENTIFICATION OF TISSUE TRANSGLUTAMINASE AS THE AUTOANTIGEN OF CELIAC-DISEASE

Celiac disease is characterized by small intestinal damage with loss o f absorptive villi and hyperplasia of the crypts, typically leading to malabsorption(1). In addition to nutrient deficiencies, prolonged cel iac disease is associated with an increased risk for malignancy, espec ially intestinal T-cell lymphoma(1-3). 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 w hich involves an immunological process in individuals with a genetic p redisposition. However, the mechanism responsible for the small intest inal damage characteristic of celiac disease is still under debate(4-6 ). Small intestinal biopsy with the demonstration of a flat mucosa whi ch is reversed on a gluten-free diet is considered the main approach f or diagnosis of classical celiac disease(7). In addition, IgA antibodi es against gliadin and endomysium, a structure of the smooth muscle co nnective tissue, are valuable tools for the detection of patients with celiac disease and for therapy control(7-9). Incidence rates of child hood celiac disease range from 1:300 in Western Ireland to 1:4700 in o ther European countries(10-12), and subclinical cases detected by sero logical screening revealed prevalences of 3.3 and 4 per 1000 in Italy and the USA, respectively IgA antibodies to endomysium are particularl y specific indicators of celiac disease(9,15), suggesting that this st ructure contains one or more target autoantigens that play a role in t he pathogenesis of the disease(16,17). However, the identification of the endomysial autoantigen(s) has remained elusive. We identified tiss ue transglutaminase as the unknown endomysial autoantigen. Interesting ly, gliadin is a preferred substrate for this enzyme, giving rise to n ovel antigenic epitopes.