Immunoreaction to xenogenic tissue in cardiac surgery: alpha-Gal and beyond
Antonio M. Calafiore, Axel Haverich, Mario Gaudino, Michele Di Mauro, Khalil Fattouch, Sotirios Prapas, Peter Zilla
Abstract
The ability of the immune system to distinguish self from non-self, reacting only to non-self, is essential for immune homeostasis. The mechanisms by which the immune system recognizes and responds to xenogenic tissue heart valves likely involve the initial activation of the innate immune system, with subsequent adaptive immune activation. The antigenicity of xenogeneic tissue constructs, primarily of porcine and bovine origin, has been extensively investigated and several antigenic epitopes have been identified. Some of them have been more exhaustively studied to avoid or at least reduce the immunoreaction triggered by their presence. Galactose-α-1,3-galactose (alpha-Gal) is a carbohydrate epitope present on the cells of all mammals (Fig. 1A). However, in ancestral Old World monkeys and apes, the gene for the enzyme alpha-1,3-galactosyltransferase, essential for the synthesis of alpha-Gal, resulted inactivated [1]. As a consequence, humans and recent Old World primates do not express the epitope. For xenotransplantation, i.e. transplantation of organs from pigs into humans, the mammals' anti-alpha-Gal antibodies represent a major immune barrier [1] (Fig. 1B).