异种移植
移植
医学
免疫学
抗体
肾移植
肾
补体系统
补体依赖性细胞毒性
流式细胞术
狒狒
内科学
单克隆抗体
抗体依赖性细胞介导的细胞毒性
作者
Yu Hisadome,Daniel Eisenson,Michelle R. Santillan,Hayato Iwase,Kazuhiko Yamada
出处
期刊:Transplantation
[Ovid Technologies (Wolters Kluwer)]
日期:2024-03-19
被引量:2
标识
DOI:10.1097/tp.0000000000004958
摘要
Xenotransplantation using pig organs is now a clinical reality. However, the process for xenograft recipient screening lacks clarity and scientific rigor: no established thresholds exist to determine which levels of preformed antipig natural antibodies (Nabs) will be safe for clinical xenograft transplantation, and hyperacute rejection (HAR) or acute humoral xenograft rejection (AHXR), which still impacts pig-to-primate kidney xenograft survivals, may impede broader application of pig-to-human clinical xenograft transplantation.We retrospectively examined 28 cases of pig-to-baboon kidney xenotransplantation using GalTKO±human complement regulatory protein (hCRP)-transgenic (Tg) pig donors, as well as 6 cases of triple-KO multi-Tg (10GE) pig donors, and developed screening algorithms to predict risk of HAR/AHXR based on recipient antipig Nab levels. Preformed Nabs were evaluated using both complement-dependent cytotoxicity and antibody (IgM and IgG) binding flow-cytometry assays.High complement-dependent cytotoxicity was associated with HAR/AHXR as expected. However, we also found that high levels of IgG were independently associated with HAR/AHXR, and we developed 2 indices to interpret and predict the risk of IgG-mediated HAR/AHXR.Based on the data in this study, we have established a new 2-step screening, which will be used for future clinical kidney xenotransplantation trials.
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