Identification of tissue transglutaminase as the autoantigen of celiac disease

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Abstract

Celiac disease is characterized by small intestinal damage with loss of absorptive villi and hyperplasia of the crypts, typically leading to malabsorption1. In addition to nutrient deficiencies, prolonged celiac disease is associated with an increased risk for malignancy, especially intestinal T-cell lymphoma1–3. 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 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 debate4–6. 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 disease7. 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 control7–9. Incidence rates of childhood celiac disease range from 1:300 in Western Ireland to 1:4700 in other European countries10–12, and subclinical cases detected by serological screening revealed prevalences of 3.3 and 4 per 1000 in Italy and the USA, respectively13,14. IgA antibodies to endomysium are particularly specific indicators of celiac disease9,15, suggesting that this structure contains one or more target autoantigens that play a role in the pathogenesis of the disease16,17. 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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Research Laboratories of ScheringAG, 13342, Berlin, Germany

Istituto di Clinical Medical generale e Terapia Medica, Policlinico S.Orsola, via Massarenti 9, 40138, Bologna, Italy

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