Xenoantigens and Xenoantibodies: Their Modification

Abstract. The hyperacute rejection of pig organs by primates, including humans, results from antibody-mediated complement activation. Protection from complement injury still leads to delayed rejection, which results from other mechanisms that may also be dependent on the presence of antibody. Anti-pig antibodies are directed largely, if not entirely, against α-galactose (αGal) epitopes on pig vascular endothelium. Prevention of antibody–antigen binding is being attempted by methods that (1) alter antigen expression on the donor organ or (2) deplete the potential recipient of anti-αGal antibody. To date, most progress has been made in depleting antibody by extracorporeal immunoadsorption using immunoaffinity columns of synthetic αGal oligosaccharides. A pig organ transplanted into a recipient baboon depleted of antibody functions for several days—in contrast to minutes to hours in unmodified baboons. The return of antibody, however, results in rejection of the graft. Pharmacologic immunosuppressive agents are relatively ineffective for prolonged suppression of anti-αGal production. Total-body irradiation and splenectomy are proving more successful. Studies are continuing with the aim of achieving a state of B cell tolerance toward αGal epitopes.