Xenoantigens and xenoantibodies: their modification.
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 alpha-galactose (alpha Gal) 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-alpha Gal antibody. To date, most progress has been made in depleting antibody by extracorporeal immunoadsorption using immunoaffinity columns of synthetic alpha Gal 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-alpha Gal 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 alpha Gal epitopes.
Cooper
D K
DK
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
Thall
A D
AD
D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D015478:Antigens, Heterophile / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D016377:Organ Transplantation; D010215:Papio; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D000910:Antibodies, Heterophile; D015478:Antigens, Heterophile