2005
DOI: 10.1038/nm1330
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Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

Abstract: We transplanted kidneys from alpha1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation… Show more

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Cited by 321 publications
(292 citation statements)
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“…While treatment with immunosuppressive drugs has shown substantial progress in allotransplantation, there are currently no immunosuppressive drugs capable of preventing xenograft rejection in a pig-to-nonhuman primate transplantation model (1,6,7). Furthermore, current immunosuppressive protocols that prevent xenograft rejection in nonhuman primates are too toxic for patient use.…”
mentioning
confidence: 99%
“…While treatment with immunosuppressive drugs has shown substantial progress in allotransplantation, there are currently no immunosuppressive drugs capable of preventing xenograft rejection in a pig-to-nonhuman primate transplantation model (1,6,7). Furthermore, current immunosuppressive protocols that prevent xenograft rejection in nonhuman primates are too toxic for patient use.…”
mentioning
confidence: 99%
“…Currently, insufficient long-term graft function prevents the successful clinical application of xenotransplantation (2). Nevertheless, advances in preventing hyperacute rejection in preclinical nonhuman primate models using genetically engineered pigs as organ source indicate that all coagulation disorders, Abs to non-Gal Ags, and cellular immunity play a role in xenogeneic responses (3)(4)(5). There are also several lines of evidence that NK cells may be a factor in delayed rejection of porcine xenografts (6).…”
mentioning
confidence: 99%
“…These pigs have been generated by targeted disruption (knockout) of the 1,3galactosyltransferase gene (Phelps et al, 2003;KoblerSimond et al, 2004;Yamada et al, 2005;Takahagi et al, 2005;McGregor et al, 2011). These pigs lack -gal epitopes and their organs do not induce an anti-Gal response when transplanted into primates (Chen et al, 2005;Ezzelarab et al, 2006;Hisashi et al, 2008;Yeh et al, 2010). Thus, in contrast to rapid (hyperacute) rejection of wild type (WT) pig organs in monkeys (observed within <1h to several hours), pig organs from 1,3galactosyltransferase knockout pigs (1,3GT KO pigs) survive in monkeys for weeks to several months prior to rejection Chen et al, 2005;Kuwaki et al, 2005;Tseng et al, 2005;Hisashi et al, 2008).…”
Section: Elimination Of the Anti-gal Ab Barrier By The Use Of 13galmentioning
confidence: 99%
“…These pigs lack -gal epitopes and their organs do not induce an anti-Gal response when transplanted into primates (Chen et al, 2005;Ezzelarab et al, 2006;Hisashi et al, 2008;Yeh et al, 2010). Thus, in contrast to rapid (hyperacute) rejection of wild type (WT) pig organs in monkeys (observed within <1h to several hours), pig organs from 1,3galactosyltransferase knockout pigs (1,3GT KO pigs) survive in monkeys for weeks to several months prior to rejection Chen et al, 2005;Kuwaki et al, 2005;Tseng et al, 2005;Hisashi et al, 2008). In the absence of anti-Gal response the next immune obstacle in xenotransplantation became apparent-the production of anti-non gal Abs against xenoantigens of the graft which are not -gal epitopes.…”
Section: Elimination Of the Anti-gal Ab Barrier By The Use Of 13galmentioning
confidence: 99%
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