The anti-nonGal xenoantibody response to alpha1,3-galactosyltransferase gene knockout pig xenografts.
The anti-nonGal xenoantibody response to alpha1,3-galactosyltransferase gene knockout pig xenografts.
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DOI：
10.1097/mot.0b013e328336b854
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发表时间：
2010-04
影响因子：
2.2
通讯作者：
Kearns-Jonker M
中科院分区：
文献类型：
--
作者：
Harnden I;Kiernan K;Kearns-Jonker M
Anti-non-gal xenoantibodies are a major barrier to the survival of genetically modified porcine xenografts. This review summarizes new information on the contribution of anti-non-gal xenoantibodies to the activation of porcine endothelial cells and the pathology of rejection and further provides an update on recent advancements in defining the unique features of anti-non-gal xenoantibody structure. Anti-non-gal xenoantibodies pre-exist at low levels in humans and non-human primates, and are notably absent in neonates. Exposure of non-human primates to α1,3 galactosyltransferase gene knockout (GalTKO) endothelial cells initiates an induced xenoantibody response that is restricted and encoded by the germline progenitor IGHV3-21. The target xenoantigen remains undetermined, but several candidate targets have been proposed, including carbohydrate xenoantigens. New advancements in molecular modeling provide insight on the mechanism by which xenoantibodies bind to structurally related carbohydrates. Genetic manipulation of porcine donors has significantly prolonged the survival of grafts placed into non-human primate recipients, but anti-non-gal xenoantibodies and thrombosis limit the ability of these grafts to function on a long term basis. Recent developments defining pre-existing anti-non-gal xenoantibody levels, the restriction in the anti-non-gal xenoantibody response and the identification of key sites defining xenoantibody/carbohydrate interactions now provide the information necessary to develop new approaches to preventing xenoantibody-mediated rejection.
