Abstract
The endomysial antibody (EMA) immunofluorescent test is a highly specific method to detect disease-specific autoantibodies in celiac disease (CD) by their binding to natural transglutaminase-2 autoantigen in tissue sections, and it is used as a compulsory confirmatory test in the non-invasive diagnosis of CD. The classical EMA substrates are the monkey esophagus and the human umbilical cord. It is increasingly difficult to use these tissues due to ethical concerns and animal welfare regulations. In this study, we developed, in cell culture, an endomysium-type extracellular biomatrix assembled by human umbilical cord vein-derived endothelial cells which binds CD antibodies in a similar pattern as monkey esophagus and has similar macromolecular composition. Evaluating retrospectively and prospectively tested patient cohorts, including 130 CD cases and 105 non-celiac controls, IgA-class celiac antibody detection on the biomatrix was equally specific (100%) as EMA testing on tissues, and had higher sensitivity (95.6% versus 91.2%). Both EMA tests were less sensitive, but more specific than transglutaminase-based ELISA measurements. The decellularization of the biomatrix improved sensitivity, enabled the detection of IgG-class celiac antibodies, and allowed for simple reading without previous training. This easily available cell-assembled biomatrix substrate may replace substrate tissues in diagnostic EMA testing in the future.