Department of Surgery, Duke University, Durham, North Carolina, USA.
Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA.
Am J Transplant. 2021 Feb;21(2):766-775. doi: 10.1111/ajt.16263. Epub 2020 Sep 12.
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.
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。