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Early reduction of regulatory T cells is associated with acute rejection in liver transplantation under tacrolimus-based immunosuppression with basiliximab induction.
American Journal of Transplantation ( IF 8.8 ) Pub Date : 2020-01-22 , DOI: 10.1111/ajt.15789
Ji Won Han 1 , Dong Jin Joo 2 , Jong Hoon Kim 1, 3 , Min-Seok Rha 1 , June Young Koh 1 , Hye Jung Park 4 , Jae Geun Lee 2 , Myoung Soo Kim 2 , Soon Il Kim 2 , Eui-Cheol Shin 1 , Jun Yong Park 4 , Su-Hyung Park 1
Affiliation  

Regulatory T (Treg) cells are important in preventing acute rejection (AR) in solid organ transplantation, but the clinical relevance of the different kinetics early after liver transplantation (LT) in acute rejectors and non‐rejectors is unclear. We analyzed peripheral blood samples of 128 LT recipients receiving basiliximab induction plus tacrolimus immunosuppression. Samples were obtained at pretransplant, D7, and D30 after LT. Frequency and phenotype of Tregs were analyzed by flow cytometry. The predictive value of Treg frequency at D7 was assessed for suspected acute rejection (SAR) and was validated for biopsy‐proven AR (BPAR). We found that the frequencies of total and activated Tregs at D7 were significantly lower in recipients with SAR and BPAR. Treg was more reduced in BPARs by in vitro tacrolimus treatment in the presence of basiliximab. Moreover, an early reduction of Treg frequency in rejectors was associated with a greater increase in Treg apoptosis and further attenuated IL‐2 signaling. D7 Treg frequency was an independent risk factor for SAR, which was also validated for BPAR. In conclusion, first‐week peripheral blood Treg frequency correlates with AR after LT under tacrolimus‐based immunosuppression, which needs to be proven in larger, geographically and clinically diverse populations.

中文翻译:

在基于他克莫司的免疫抑制和巴利昔单抗诱导下,调节性 T 细胞的早期减少与肝移植中的急性排斥反应有关。

调节性 T (Treg) 细胞在预防实体器官移植中的急性排斥反应 (AR) 方面很重要,但肝移植 (LT) 后早期不同动力学在急性排斥反应和非排斥反应中的临床相关性尚不清楚。我们分析了 128 名接受巴利昔单抗诱导加他克莫司免疫抑制的 LT 接受者的外周血样本。在移植前、D7 和 LT 后的 D30 获得样品。通过流式细胞术分析 Tregs 的频率和表型。评估 D7 时 Treg 频率对疑似急性排斥反应 (SAR) 的预测价值,并针对活检证实的 AR (BPAR) 进行验证。我们发现在 D7 时总 Tregs 和激活 Tregs 的频率在 SAR 和 BPAR 接受者中显着降低。在存在巴利昔单抗的情况下,通过体外他克莫司处理,BPAR 中的 Treg 减少更多。此外,排斥反应中 Treg 频率的早期降低与 Treg 细胞凋亡的增加有关,并进一步减弱了 IL-2 信号。D7 Treg 频率是 SAR 的独立危险因素,这在 BPAR 中也得到了验证。总之,第一周外周血 Treg 频率与基于他克莫司的免疫抑制 LT 后的 AR 相关,这需要在更大的、地理上和临床上不同的人群中得到证明。
更新日期:2020-01-22
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