Binding of human natural antibodies to nonαGal xenoantigens on porcine erythrocytes

Background Xenotransplantation is considered one of possible solutions for the serious shortage of organs and cells in transplantation. Although the alpha Gal epitope (Gal alpha 1,3Gal beta 1,4GlcNAc-R) has been identified as being a major xenoantigen responsible for hyperacute rejection, the removal of anti-alpha Gal antibody alone from human serum is insufficient to circumvent antibody-mediated immune responses. Methods and Results, We report here the characterization of xenoreactive human natural antibodies against antigens without the alpha Gal epitope (non alpha Gal xenoantigens) on porcine erythrocytes using flow cytometry and the evidence for their involvement in complement-mediated hemolysis. Furthermore, a novel protein of 45-kDa has been isolated from the porcine erythrocyte membrane as a major protein antigen recognized by human anti-non alpha Gal. Conclusion. The data presented here will add to our knowledge of xenoantigens on porcine red cells and be important for developing strategies to produce modified red cells immunologically compatible to humans.