Binding of human natural antibodies to non alpha Gal xenoantigens on porcine erythrocytes

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