Failure to deplete anti‐Galα1‐3Gal antibodies after pig‐to‐baboon organ xenotransplantation by immunoaffinity columns containing multiple Galα1‐3Gal oligosaccharides

Abstract

The EIA reduces anti-alphaGal and APHA antibodies, preventing the HAR of non-transgenic pig hearts transplanted in baboons, as does hDAF expression. However, EIA does not modify the level of anti-alphaGal IgM and APHA antibodies after Tx nor the AHXR of either non-transgenic or hDAF pig organs. The increase in anti-alphaGal IgM after Tx was similar for the different antibodies of the anti-alphaGal polymorphism, and was only partially neutralized in vitro with the specific alphaGal oligosaccharide.

Potential of an Injectable Polymer to Prevent Hyperacute Rejection of Ex Vivo Perfused Porcine Lungs

“…Approaches to eliminate antiporcine antibodies in pigto-primate transplantation have included plasmapheresis (34), extracorporal immunoabsorption of immunoglobulins (35), or selective extracorporal immunophoresis removing antipig (36), or anti-␣-Gal antibodies (3,31,32). The effects, however, were transient since antibodies are continuously produced and were associated with complications (15).…”

“…Primates have a polymorphism of the anti-␣-Gal antibody population against ␣-Gal disaccharides, trisaccharides one, two, and six and pentasaccharides (30). Columns containing multiple ␣-Gal oligosaccharides have been applied in xenotransplantation with moderate success (31,32). More complete removal of ␣-Gal antibodies was achieved when two different polymers were combined in a column, suggesting that a combination of additional polymers carrying different ␣-Gal structures may be more effective in antibody absorption (13).…”

“…However, by means of this assay, we were not able to detect a significant absorbance of the remaining antiporcine antibodies in the subsequent perfusion of a lung xenograft. It has been proposed, that these remaining antibodies, including non ␣-Gal antibodies, may not be relevant in HAR (32,33). In recipient cynomolgus monkeys, levels of non ␣-Gal antibodies were considered negligible prior to transplantation.…”

Antibody Mediated Rejection in Pig-To-Nonhuman Primate Xenotransplantation Models

“…In a study of immunosuppressed cynomolgus monkey recipients of cardiac xenografts, Lam and colleagues could demonstrate a considerable increase of both IgM and IgG anti-non-αGal antibodies in all animals with AHXR in the graft, whilst no relevant changes in the titers were shown in animals that did not reject their transplant [78]. In another series, it was shown that repeated extracorporeal immunoadsorptions, using an αGal column containing disaccharides, type 2 trisaccharides and pentasaccharides failed to deplete antiαGal antibodies in baboon recipients of a porcine xenograft [97]. Similarly, Buhler and colleagues could show that exposure of baboons to porcine antigens resulted in the production of anti-αGal and anti-non-αGal antibodies [39].…”

Pig-to-nonhuman primate organ xenotransplantation

“…Manez et al [6] demonstrated that extracorporeal immunoadsorption of anti-Gal antibodies in baboons, using immunoaffinity columns containing various Gal oligosaccharides, reduced anti-Gal antibody levels and prevented hyperacute rejection. The level of anti-Gal immunoglobulin M after nontransgenic or hDAF pig heart transplantation was not significantly modified, however, nor was the occurrence of AHXR.…”