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抗胸腺细胞球蛋白与 T 细胞表型及儿科肾移植临床结局的关系。

Relationship between antithymocyte globulin, T cell phenotypes, and clinical outcomes in pediatric kidney transplantation.

机构信息

Department of Surgery, Duke University, Durham, North Carolina, USA.

Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA.

出版信息

Am J Transplant. 2021 Feb;21(2):766-775. doi: 10.1111/ajt.16263. Epub 2020 Sep 12.

Abstract

Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Pediatric Transplant (IMPACT) study, we compared T cell phenotypes after ATG or non-ATG induction. We examined the effects of ATG on the early clinical outcomes of alloimmune events (development of de novo donor specific antibody and/or biopsy proven rejection) and infection events (viremia/viral infections). Long-term patient and graft outcomes were examined using the Scientific Registry of Transplant Recipients. After ATG induction, although absolute counts of CD4 and CD8 T cells were lower, patients had higher percentages of CD4 and CD8 memory T cells with a concomitant decrease in frequency of naïve T cells compared to non-ATG induction. In adjusted and unadjusted models, ATG induction was associated with increased early event-free survival, with no difference in long-term patient or allograft survival. Decreased CD4 naïve and increased CD4 effector memory T cell frequencies were associated with improved clinical outcomes. Though immunologic parameters are drastically altered with ATG induction, long-term clinical benefits remain unclear in pediatric patients.

摘要

使用抗胸腺细胞球蛋白 (ATG) 进行耗竭性诱导可降低成人肾移植受者急性排斥反应的发生率,但对儿童的影响知之甚少。本研究使用 Immune Development in Pediatric Transplant (IMPACT) 研究中的 103 例患者的纵向队列,比较了 ATG 或非 ATG 诱导后的 T 细胞表型。我们研究了 ATG 对同种免疫事件(新出现的供体特异性抗体和/或活检证实的排斥反应的发展)和感染事件(病毒血症/病毒感染)的早期临床结局的影响。使用移植受者科学注册处来检查长期的患者和移植物结局。ATG 诱导后,尽管 CD4 和 CD8 T 细胞的绝对计数较低,但与非 ATG 诱导相比,患者的 CD4 和 CD8 记忆 T 细胞的百分比更高,而幼稚 T 细胞的频率降低。在调整和未调整的模型中,ATG 诱导与早期无事件生存率增加相关,与长期患者或移植物生存率无差异。CD4 幼稚细胞减少和 CD4 效应记忆 T 细胞频率增加与改善的临床结局相关。尽管 ATG 诱导会极大地改变免疫参数,但在儿科患者中,长期的临床获益仍不清楚。

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