Abstract

Background & Aims: Celiac disease is characterized by disturbed jejunal crypt-villus axis biology with immunoglobulin (Ig) A deposits underlining the epithelium. The aim of this study was to test whether celiac disease serum IgA (reticulin/endomysial autoantibodies) interferes with the mesenchymal-epithelial cell cross-talk. Methods: Differentiation of T84 epithelial cells was induced with IMR-90 fibroblasts or transforming growth factor β in three-dimensional collagen gel cultures. The effects of purified celiac IgA and monoclonal tissue transglutaminase antibodies (CUB7402) were studied by adding the antibodies to the cocultures. Results: Active celiac disease IgA, reactive for tissue transglutaminase, significantly inhibited T84 epithelial cell differentiation ( P < 0.001) and increased epithelial cell proliferation ( P = 0.024). Similar effects were obtained with antibodies against tissue transglutaminase. Conclusions: Celiac disease–associated IgA class antibodies disturb transforming growth factor β–mediated fibroblast–epithelial cell cross-talk in this in vitro crypt-villus axis model. This primary finding indicates that celiac disease–specific autoantibodies may also contribute to the formation of the gluten-triggered jejunal mucosal lesion in celiac disease. GASTROENTEROLOGY 1999;116:566-572

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