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肾移植受者感染发生的白细胞转录组指标。

Leukocyte transcriptome indicators of development of infection in kidney transplant recipients.

机构信息

Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

出版信息

Clin Transplant. 2021 Apr;35(4):e14252. doi: 10.1111/ctr.14252. Epub 2021 Mar 5.

Abstract

After kidney transplantation, infection and death are important clinical complications, especially for the growing numbers of older patients with limited resilience to withstand adverse events. Evaluation of changes in gene expression in immune cells can reveal the underlying mechanisms behind vulnerability to infection. A cohort of 60 kidney transplant recipients was evaluated. Gene expression in peripheral blood mononuclear cells 3 months after kidney transplantation was analyzed to compare differences between patients with infection and those who were infection-free in the first-year post-transplant. Pro-inflammatory genes such as IL1B, CCL4, and TNF were found to be downregulated in post-transplant PBMC from patients who developed infection. In contrast, genes involved in metabolism, HLA genes, and transcripts involved in type I interferon innate antiviral responses were found to be upregulated. Promoter-based bioinformatic analyses implicated increased activity of interferon regulatory factors, erythroid nuclear factor (E2), and CCAAT-enhancer-binding protein (C/EBP) in patients who developed infections. Differential patterns of gene expression were observed in patients who developed infection after kidney transplantation, with patterns distinct from changes associated with patient age, suggesting possible mechanisms behind vulnerability to infection. Assessment of gene expression in blood may offer an approach for patient risk stratification and monitoring after transplantation.

摘要

肾移植后,感染和死亡是重要的临床并发症,尤其是对于越来越多的老年患者,他们的抵抗力有限,难以承受不良事件的影响。评估免疫细胞中基因表达的变化可以揭示易感染的潜在机制。本研究评估了 60 例肾移植受者。分析了肾移植后 3 个月外周血单个核细胞中的基因表达,以比较移植后第 1 年内发生感染和未发生感染的患者之间的差异。结果发现,发生感染的患者移植后 PBMC 中的促炎基因(如 IL1B、CCL4 和 TNF)表达下调。相比之下,参与代谢的基因、HLA 基因以及 I 型干扰素固有抗病毒反应的转录本表达上调。基于启动子的生物信息学分析表明,感染患者的干扰素调节因子、红细胞核因子(E2)和 CCAAT 增强子结合蛋白(C/EBP)的活性增加。肾移植后发生感染的患者观察到基因表达的差异模式,与与患者年龄相关的变化模式不同,提示易感染的潜在机制。血液中基因表达的评估可能为移植后患者的风险分层和监测提供一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1636/9341289/3b62e0521d2a/nihms-1682921-f0001.jpg

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本文引用的文献

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OPTN/SRTR 2018 Annual Data Report: Kidney.OPTN/SRTR 2018 年度数据报告:肾脏。
Am J Transplant. 2020 Jan;20 Suppl s1:20-130. doi: 10.1111/ajt.15672.
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Differences in Gene Expression in Older Compared With Younger Kidney Transplant Recipients.老年与年轻肾移植受者的基因表达差异
Transplant Direct. 2019 Mar 4;5(4):e436. doi: 10.1097/TXD.0000000000000870. eCollection 2019 Apr.
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Reduced dynamic range of antiviral innate immune responses in aging.衰老导致抗病毒先天免疫反应的动态范围缩小。
Exp Gerontol. 2018 Jul 1;107:130-135. doi: 10.1016/j.exger.2017.08.019. Epub 2017 Aug 16.

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