The problem of anti-pig antibodies in pig-to-primate xenografting: current and novel methods of depletion and/or suppression of production of anti-pig antibodies.
The role of antibodies directed against Galalpha1-3Gal (alpha-Gal) epitopes in porcine-to-primate xenotransplantation has been widely studied during the past few years. These antibodies (anti-alpha-Gal) have been associated with both hyperacute rejection and acute vascular rejection of vascularized organs. Depletion and (temporary or permanent) suppression of production of anti-alpha-Gal seem to be essential to the long-term survival of these organs, even when the ultimate aim is accommodation or tolerance. Although more than 95% depletion of anti-alpha-Gal can be achieved by the use of immunoaffinity column technology, to date no regimen has been successful in preventing the return of anti-alpha-Gal (from continuing production). In this review, we discuss current and novel methods for achieving depletion or inhibition (i.e. extracorporeal immunoadsorption, anti-idiotypic antibodies, the intravenous infusion of immunoglobulin or oligosaccharides) and suppression of production (i.e. irradiation, pharmacologic agents, specific monoclonal antibodies, immunotoxins) of anti-alpha-Gal antibodies.
Alwayn
I P
IP
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
Basker
M
M
Buhler
L
L
Cooper
D K
DK
D000818:Animals; D000917:Antibody Formation; D004187:Disaccharides / Q000037:antagonists & inhibitors* / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D016377:Organ Transplantation; D011323:Primates; D013552:Swine; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
D004187:Disaccharides; D000939:Epitopes; C055075:galactosyl-(1-3)galactose