Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients.
Peripheral phenotype and gene expression profiles of combined liver-kidney transplant patients.
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DOI：
10.1111/liv.12917
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Conchon S
中科院分区：
文献类型：
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作者：
Dumontet E;Danger R;Vagefi PA;Londoño MC;Pallier A;Lozano JJ;Giral M;Degauque N;Soulillou JP;Martínez-Llordella M;Lee H;Latournerie M;Boudjema K;Dulong J;Tarte K;Sanchez-Fueyo A;Feng S;Brouard S;Conchon S
在联合移植中已经报道了一种移植物对另一种移植物的有益作用，但是每种移植物的相关机制和生物学影响尚未建立。在多重分析中，我们探索了来自总共235名患者的PBMC表型和45种免疫相关信使RNA和754种microRNA的特征，包括肝肾联合移植受者（CLK）、仅在经典免疫抑制下进行肝脏（L-STA）或肾脏（K-STA）移植的患者以及耐受肝脏（L-TOL）或肾脏移植（K-TOL）的患者。CLK组外周血CD 19 + CD 24 + CD 38低记忆B细胞和Helios+ Treg细胞比例高于L-STA组和K-STA组（P < 0.05，P < 0.01）。CLK与K-STA中很少有miRNA显著差异表达，与L-STA相比甚至更少（35和8，P < 0.05）。最后，预测CLK与K-TOL共享共同的miRNA靶点，甚至与L-TOL共享更多靶点（344和411，P = 0.005）。总的来说，CLK显示中间表型和基因谱，这是更接近肝移植患者，与耐受患者的配置文件可能有相似之处。这些数据表明，CLK患者显示出两种同种异体移植物的免疫影响，其中肝脏的影响更大。
The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established. In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver–kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL). CLK show an intermediary phenotype with a higher percentage of peripheral CD19+CD24+CD38Low memory B cells and Helios+ Treg cells, two features associated with tolerance profiles, compared to L-STA and K-STA (P < 0.05, P < 0.01). Very few miRNA were significantly differentially expressed in CLK vs. K-STA and even fewer when compared to L-STA (35 and 8, P < 0.05). Finally, CLK are predicted to share common miRNA targets with K-TOL and even more with L-TOL (344 and 411, P = 0.005). Altogether CLK display an intermediary phenotype and gene profile, which is closer to that of liver transplant patients, with possible similarities with the profiles of tolerant patients. These data suggest that CLK patients show the immunological influence of both allografts with liver having a greater influence.