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单次剂量兔抗胸腺细胞球蛋白和阿仑单抗导致的淋巴细胞耗竭时间延长在肾移植中的作用。

Prolonged lymphocyte depletion by single-dose rabbit anti-thymocyte globulin and alemtuzumab in kidney transplantation.

机构信息

DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida 33136, USA.

出版信息

Transpl Immunol. 2011 Sep;25(2-3):104-11. doi: 10.1016/j.trim.2011.07.002. Epub 2011 Jul 19.

Abstract

Although antibody induction has gained in popularity, two agents are rarely combined. We retrospectively analyzed peripheral lymphocyte phenotypes of renal transplant recipients who received induction therapy with a different antibody/combination: alemtuzumab(C1H), Thymoglobulin(rATG), daclizumab(Dac), rATG+C1H, and rATG+Dac. CD4+ T-cells were suppressed by C1H and rATG+C1H, as well as by rATG and rATG+Dac but to a lesser extent. The effect lasted for 3 years at around 40% of baseline values. CD8+ T-cells showed a similar trend but had a more rapid recovery to baseline. CD19+ B-cells were effectively suppressed for 2 months by C1H and rATG+C1H, and abruptly returned to baseline afterwards; suppression by rATG(7 doses) was modest but lasted longer. A higher proportion of CD56+CD16+ Natural Killer cells in C1H treated patients suggested a relatively spared effect of C1H on this cell type. Low CD25+ T-cells by 5-dose Dac returned to baseline around 6 months, whereas rATG+C1H and rATG+Dac showed persistent effect. CD4+CD25hi T-cells were suppressed by both rATG+C1H and rATG+Dac, but the initial proportion of CD4+CD25hi T-cells among CD4+ T-cells and CD4+CD25hi/CD4+CD25lo ratio were significantly higher in rATG+C1H. Overall, with extensive and persistent lymphocyte suppression by a simple administration of agents, single-dose rATG+C1H induction can be an alternative in renal transplantation.

摘要

虽然抗体诱导已越来越受欢迎,但很少有两种药物联合使用。我们回顾性分析了接受不同抗体/联合诱导治疗的肾移植受者的外周淋巴细胞表型:阿仑单抗(C1H)、胸腺球蛋白(rATG)、达珠单抗(Dac)、rATG+C1H 和 rATG+Dac。C1H 和 rATG+C1H 以及 rATG 和 rATG+Dac 可抑制 CD4+T 细胞,但抑制程度较低,作用可持续 3 年,约为基线值的 40%。CD8+T 细胞呈相似趋势,但恢复至基线更快。C1H 和 rATG+C1H 可有效抑制 CD19+B 细胞 2 个月,之后迅速恢复至基线;rATG(7 剂)的抑制作用较弱,但持续时间较长。C1H 治疗患者中 CD56+CD16+自然杀伤细胞的比例较高,表明 C1H 对该细胞类型的相对保护作用。5 剂 Dac 可使低 CD25+T 细胞在 6 个月左右恢复至基线,而 rATG+C1H 和 rATG+Dac 则持续有效。rATG+C1H 和 rATG+Dac 均可抑制 CD4+CD25hiT 细胞,但 rATG+C1H 中 CD4+T 细胞和 CD4+CD25hi/CD4+CD25lo 比值中 CD4+CD25hiT 细胞的初始比例显著较高。总之,通过简单给药可广泛且持续抑制淋巴细胞,单剂量 rATG+C1H 诱导可能是肾移植的一种替代方法。

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