Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans
Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans
复制标题
DOI：
10.1111/j.1399-3089.2006.00319.x
复制
发表时间：
2006-07-01
影响因子：
3.9
通讯作者：
Cooper, David K. C.
中科院分区：
文献类型：
--
作者：
Hara, Hidetaka;Ezzelarab, Mohamed;Cooper, David K. C.
背景资料：α 1，3-半乳糖基转移酶基因敲除（GT-KO）纯合子猪的可用性使得能够研究针对Gal α 1，3Gal（Gal）以外的抗原（称为非Gal抗原）的灵长类抗体的发生率和细胞毒性。来自27名健康人和31名等待同种异体肾移植的患者的血清，通过流式细胞术测试未致敏的[群体反应性抗体（PRA）< 10%]或同种异体致敏的（PRA > 70%）猪的免疫球蛋白M（IgM）和IgG与来自野生型（WT）和GT-KO猪的外周血单核细胞（PBMC）的结合。结果：27份健康人血清中IgM和IgG均能与WT PBMC结合，而与GT KO PBMC结合的IgM和IgG分别占78%和63%。与WT PBMC的平均结合显著大于GT-KO PBMC。而100%的血清对WT PBMC具有细胞毒性，仅61%的血清对GT-KO PBMC具有细胞毒性，并且裂解程度显著较小。未致敏和同种致敏血清对WT和GT-KO PBMC的IgM和IgG的平均结合率和细胞毒性与健康血清均无显著差异。超过一半的健康人测试有细胞毒性抗体GT-KO PBMC，但同种异体致敏的患者将不会有更大的风险排斥猪异种移植的体液机制。
Background: The availability of pigs homozygous for alpha 1,3-galactosyltransferase gene-knockout (GT-KO) has enabled study of the incidence and cytotoxicity of primate antibodies directed to antigens other than Gal alpha 1,3Gal (Gal), termed non-Gal antigens.Methods: Sera from 27 healthy humans and 31 patients awaiting renal allotransplantation, who were either unsensitized [panel reactive antibodies (PRA) < 10%] or allosensitized (PRA > 70%), were tested by flow cytometry for binding of immunoglobulin M (IgM) and IgG to peripheral blood mononuclear cells (PBMC) from both wild-type (WT) and GT-KO pigs. Complement-dependent cytotoxicity to WT and GT-KO PBMC was also measured.Results: IgM and IgG from all 27 (100%) healthy human sera bound to WT PBMC, while 78% and 63% of these sera had IgM and IgG that bound to GT-KO PBMC, respectively. Mean binding to WT PBMC was significantly greater than GT-KO PBMC. Whereas 100% of sera were cytotoxic to WT PBMC, only 61% were cytotoxic to GT-KO PBMC, and the extent of lysis was significantly less. Neither mean binding of IgM and IgG nor cytotoxicity of unsensitized and allosensitized sera to WT and GT-KO PBMC was significantly different to that of healthy sera.Conclusion: More than half of the healthy humans tested had cytotoxic antibodies to GT-KO PBMC, but allosensitized patients will be at no greater risk of rejecting a pig xenograft by a humoral mechanism.