Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance.
Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance.
复制标题
诱导治疗对与排斥和耐受性相关的分子标记的表达的影响。
DOI：
10.1186/s12882-015-0141-2
复制
发表时间：
2015-08-19
期刊：
影响因子：
2.3
通讯作者：
Viklicky O
中科院分区：
文献类型：
--
作者：
Krepsova E;Tycova I;Sekerkova A;Wohlfahrt P;Hruba P;Striz I;Sawitzki B;Viklicky O
诱导治疗可以改善肾移植（KTx）的结果，但对其作用机制知之甚少。前瞻性监测60例肾移植受者KTx前、后7、14、21、28、60、90 d、6个月和12个月外周血中与耐受或排斥相关的T细胞相关基因（CD 247、GZMB、PRF 1、FOXP 3、MAN 1A 1、TCAIM和TLR 5）和淋巴细胞亚群的mRNA水平。患者接受基于钙调神经磷酸酶的三联免疫抑制治疗，并接受兔抗胸腺细胞球蛋白（rATG，n = 24）、巴利昔单抗（n = 17）诱导或不进行诱导（无诱导，n = 19）。统计学分析采用广义线性混合模型，重复测量采用伽马分布，调整排斥反应、受体/供体年龄和延迟移植功能。rATG处理引起7天内所有T细胞类型群体和自然杀伤（NK）细胞的强烈减少，然后观察到缓慢增加和再群体。这在CD 247、FOXP 3、GZMB和PRF 1的表达水平中也被注意到。与未诱导组相比，巴利昔单抗组表现出更高的CD 247、GZMB、FOXP 3和TCAIM mRNA水平以及调节性T细胞（Treg）计数。与未诱导组相比，rATG组MAN 1A 1和TLR 5 mRNA表达水平升高，TCAIM表达水平降低。rATG诱导治疗与T细胞和NK细胞相关转录物水平降低以及KTx后不久两种排斥相关转录物（MAN 1A 1和TLR 5）上调相关。巴利昔单抗治疗与Treg细胞绝对数量增加以及FOXP 3和TCAIM表达水平增加相关。
Induction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects. The mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx. Patients were treated with calcineurin inhibitor-based triple immunosuppression and induction with rabbit anti-thymocyte globulin (rATG, n = 24), basiliximab (n = 17), or without induction (no-induction, n = 19). A generalized linear mixed model with gamma distribution for repeated measures, adjusted for rejection, recipient/donor age and delayed graft function, was used for statistical analysis. rATG treatment caused an intense reduction in all T cell type population and natural killer (NK) cells within 7 days, then a slow increase and repopulation was observed. This was also noticed in the expression levels of CD247, FOXP3, GZMB, and PRF1. The basiliximab group exhibited higher CD247, GZMB, FOXP3 and TCAIM mRNA levels and regulatory T cell (Treg) counts than the no-induction group. The levels of MAN1A1 and TLR5 mRNA expressions were increased, whereas TCAIM decreased in the rATG group as compared with those in the no-induction group. The rATG induction therapy was associated with decreased T and NK cell-related transcript levels and with upregulation of two rejection-associated transcripts (MAN1A1 and TLR5) shortly after KTx. Basiliximab treatment was associated with increased absolute number of Treg cells, and increased level of FOXP3 and TCAIM expression.