Removal Of Baboon And Human Antiporcine Igg And Igm Natural Antibodies By Immunoadsorption

Immunoaffinity removal of xenoreactive antibodies using modified dialysis or microfiltration membranes

“…One approach Watts et al, 2000;Zydney and Colton, 1986) used a centrifugal plasma separator and a column of porous silica particles containing bound ligand with a total priming volume of 300 mL. Another approach (Leventhal et al, 1995;Lin et al, 1997) used a rotary membrane plasmapheresis device followed by one or two sepharose columns with similar priming volume. Both approaches required two separate pieces of equipment for plasma separation and immunoadsorption.…”

“…Three methods have been examined in attempts to remove the xenoreactive antibodies which cause hyperacute rejection, including: 1) organ perfusion, in which blood of the host is passed through an animal organ where the xenoreactive antibodies bind to the Gal epitopes on endothelial cells (Fischel et al, 1990;Tuso et al, 1993); 2) removal of all the IgG, IgM, IgA antibodies by plasmapheresis (Alexandre et al, 1989;Besse et al, 1994;Brandt et al, 1988;Leventhal et al, 1995); and 3) immunoaffinity adsorption on bead columns (Alwayn et al, 1999;Kozlowski et al, 1998;Leventhal et al, 1995;Lin et al, 1997;Rieben et al, 1995;Taniguchi et al, 1996;Watts et al, 2000;Xu et al, 1998) using synthetic Gal epitopes (e.g., the ␣Gal trisaccharide ligand Gal␣1-3Gal␤1-4GlcNAc trisaccharide). Each of these methods has associated disadvantages.…”

Gene therapy in transplantation

“…This antibodymediated hyperacute rejection of porcine donor organs has been shown to occur in non-human primate recipients. [156][157][158] In fact, almost all of the human Abs bind to an oligosaccharide pig xenoepitope defined as Gal-␣(1,3)-Gal-␤(1,4)-GlcNAc-protein, also known as the ␣-galactosyl epitope. 159,160 Complement-mediated lysis of the xenograft occurs by the classical pathway culminating in the formation of the membrane attack complex.…”

“…In a pig-to-baboon kidney xenotransplant, removal of the Abs along with immunosuppression resulted in prolongation of graft survival up to the time killed which was 13 days after the transplant. 158 Although Ab-dependent complement activation appears to be the most important determinant of hyperacute rejection, it is possible that the alternative pathway can also be involved. Therefore, alternative strategies have been devised to inhibit or prevent hyperacute rejection in the presence of xenoreactive Abs.…”

Xenogeneic transplantation

“…The rejected organs demonstrated focal vascular changes, similar to hyperacute rejection and, more importantly, IgM deposition in the absence of complement deposition was observed on EC. Serial transplantation of organs, as well as immunoabsorption of antibody has also been attempted 34 . Although HAR was delayed in many of these experiments, antibody depletion was always temporary.…”