IgA anti-tissue transglutaminase: setting the stage for coeliac disease screening

Coeliac disease is triggered in genetically predisposed individuals by the ingestion of wheat and related cereals. Affected persons raise an intestinal mucosal T-cell response against the gluten fraction of these cereals. Furthermore, they produce characteristic circulating IgA antibodies to a self-antigen present in the extracellular matrix that can be detected on tissue sections. The positive predictive value of these endomysial, reticular or umbilical cord antibodies for coeliac disease comes close to 100%. Recently, the enzyme tissue transglutaminase was identified as the main, if not sole, endomysial autoantigen in coeliac disease. Enzyme-linked immunosorbent assay tests with tissue transglutaminase from guinea pig or the recombinant human enzyme have been established that allow a standardized and quantitative determination of IgA anti-tissue transglutaminase titres. While the published assay variants report high positive and negative predictive values for coeliac disease, they were applied to preselected patients from mostly single centres. Therefore, validation and in part cross-validation of a standardized assay based on guinea pig tissue transglutaminase in 38 European and non-European centres is timely. With a sensitivity of 90% and specificity of 96% relative to local diagnostic standards the assay performed well. Considering further improvement by the use of recombinant human tissue transglutaminase as the antigen and central re-evaluation of the local standards for confirmation of coeliac disease, this enzyme-linked immunosorbent assay promises to become the primary tool for non-invasive diagnosis, therapy control and screening of coeliac disease. However, with an estimated prevalence of 1:100-1:200 of mostly atypical and subclinical coeliacs in Western populations, we are confronted with the question of how far mass screening is ethically feasible and cost effective.