CARBOHYDRATE ANTIGENS OF PIG-TISSUES REACTING WITH HUMAN NATURAL ANTIBODIES AS POTENTIAL TARGETS FOR HYPERACUTE VASCULAR REJECTION IN PIG-TO-MAN ORGAN XENOTRANSPLANTATION

Pig tissues were screened by immunofluorescence with lectins, mAb, and human natural antibodies for the presence of carbohydrate antigens, which may be potential targets for hyperacute vascular rejection in pig to man xenotransplantation. The unfucosylated monomorph linear B-antigen was found at the surface of all porcine vascular endothelial cells. This pig linear-B antigen reacts strongly with the anti-alpha Gal isolectin B-4 from Griffonia simplicifolia 1 and with human natural anti-alpha Gal antibodies specifically purified by affinity chromatography on synthetic oligosaccharides containing the terminal nonreducing alpha Gal1->3 beta Gal-R disaccharide. This antigenic activity is destroyed by treatment of pig tissues with cu-galactosidase. The localization of this linear-B epitope on vascular endothelium and its reactivity with natural human anti-alpha Gal antibodies suggest that it may play a major role in the hyperacute vascular rejection of pig to man organ xenografts. The lectin from Maackia amurensis reacting with alpha NeuAc2->3 beta 9Gal1->4GleNAe/Gle was also positive on pig vascular endothelium, but we do not know yet whether there are human natural antibodies reacting with the carbohydrate recognized by this lectin. Epithelial cells of pig renal proximal convoluted tubules, respiratory epithelium, pancreatic duets, and epidermis express the linear-B antigen, but they are less likely to trigger a hyperacute vascular rejection because they are not directly exposed to the blood. The genetically defined pig A(+)/A(-) system controls the expression of A and H antigens in pig epithelial cells from renal distal and collecting tubules, biliary ducts, pancreatic ducts, large bronchi, and digestive mucose. The pig A antigen may trigger an immune response in human O or B recipients if they are transplanted with organs from A(+) pigs, but the pig A antigen is probably not involved in the hyperacute vascular rejection of a xenograft because it is not expressed on vascular endothelium.