Ganglioside xenoantigens in pig lymphocytes and aorta

Abstract

THE main xenoantigen in the pig-to-human species combination is the carbohydrate antigen epitope Gala1-3Gal, present on both glycoproteins and glycolipids on the cell surface. All humans have preformed antibodies reacting with this antigen epitope, and these antibodies are responsible for initiating the hyperacute rejection when pig organs are transplanted to human recipients. It is very likely that other pig xenoantigen epitopes exist that may elicit an immune response in humans upon xenografting. Examples of such epitopes are the blood group A/O antigens and the Hanganutziu-Deicher (H-D) antigen. The latter is an N-glycolyl-neuraminic acid (NeuGc) terminated ganglioside present in animals such as pig and sheep but absent in humans. Upon exposure to a pig organ, a human recipient can be immunized owing to a direct interaction with the pig tissue or from the transfer of tissue/cells from the organ into the recipient. Two patients extracorporeally connected to pig kidneys reacted with a strong humoral immune response to a short time (65 and 15 minutes, respectively) exposure to the kidney tissue. The main part of the antibodies reacted with the Gala1-3Gal xenoantigen. In addition, glycolipid binding, which could not be inhibited by soluble Gala1-3Galb1-4GlcNAc saccharide, was also detected, indicating the possibility of an immunization to other carbohydrate xenoantigens. Because exposure to the xenogenic organ was rather short, the cells/tissue responsible for the immunization might have been released from the kidneys and transported into the patients. Most likely candidates for this are damaged endothelial cells and passenger lymphocytes present in the organ. In this report we show that a considerable amount of passenger leukocytes are continuously released from pig kidneys upon perfusion with large volumes of perfusion solution. Glycolipids were isolated from pig lymphocytes and aortas (as an endothelial cell source) and a strong immunostaining to several of the ganglioside components was found in serum samples collected from one patient 3 to 4 weeks after an extracorporeal pig kidney xenoperfusion.