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肾移植受者慢性肾移植功能障碍及移植肾功能中自然杀伤细胞亚群与白细胞介素-2、白细胞介素-15和白细胞介素-18基因表达

Natural Killer Cell Subsets and IL-2, IL-15, and IL-18 Genes Expressions in Chronic Kidney Allograft Dysfunction and Graft Function in Kidney Allograft Recipients.

作者信息

Assadiasl S, Sepanjnia A, Aghili B, Nafar M, Ahmadpoor P, Pourrezagholi F, Parvin M, Shahlaee A, Nicknam M H, Amirzargar A

机构信息

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Chronic Kidney Disease Research Center, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Int J Organ Transplant Med. 2016;7(4):212-217. Epub 2016 Nov 1.

PMID:28078060
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5219582/
Abstract

BACKGROUND

While acute rejection and early graft loss rates have decreased substantially over the past four decades, progressive chronic allograft dysfunction (CAD) still remains a common cause of late graft loss in kidney transplant recipients.

OBJECTIVE

This study was conducted to investigate the percentage of natural killer (NK) cell subsets and IL-2, 15 and 18 genes expression in two groups of CAD and well-function graft (WFG) recipients.

METHODS

30 renal allograft recipients with biopsy-proven interstitial fibrosis/tubular atrophy (IF/TA) and impaired renal function, and 30 sex- and age-matched WFG patients were enrolled in this study. The percentage of NK cell subsets including NK CD56 and NK CD56 cells were determined by flowcytometry; IL-2, IL-15, and IL-18 genes expressions were assessed by real-time PCR.

RESULTS

Compared to WFG patients, there was a significant (p<0.05) increase in the percentage of NK CD56 cells in CAD patients. However, the difference in percentage of NK CD56 cells or CD56/CD56 ratio between the studied groups was not significant. In addition, IL-2, 15 and 18 genes expressions were almost similar in CAD and WFG patients.

CONCLUSION

We found higher percentages of NK CD56 subset in kidney transplant recipients with CAD without considerable changes in related cytokines' gene expression, suggesting a possible defect of NK cells maturation in these patients.

摘要

背景

尽管在过去四十年中急性排斥反应和早期移植物丢失率大幅下降,但进行性慢性移植物功能障碍(CAD)仍是肾移植受者晚期移植物丢失的常见原因。

目的

本研究旨在调查两组CAD受者和移植物功能良好(WFG)受者中自然杀伤(NK)细胞亚群的百分比以及IL-2、IL-15和IL-18基因的表达情况。

方法

本研究纳入了30例经活检证实有间质纤维化/肾小管萎缩(IF/TA)且肾功能受损的肾移植受者,以及30例年龄和性别匹配的WFG患者。通过流式细胞术测定包括NK CD56和NK CD56细胞在内的NK细胞亚群的百分比;通过实时PCR评估IL-2、IL-15和IL-18基因的表达。

结果

与WFG患者相比,CAD患者中NK CD56细胞的百分比显著增加(p<0.05)。然而,研究组之间NK CD56细胞百分比或CD56/CD56比值的差异并不显著。此外,CAD患者和WFG患者中IL-2、IL-15和IL-18基因的表达几乎相似。

结论

我们发现CAD肾移植受者中NK CD56亚群的百分比更高,而相关细胞因子的基因表达没有显著变化,这表明这些患者的NK细胞成熟可能存在缺陷。

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引用本文的文献

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Decreased NK cell immunity in kidney transplant recipients late post-transplant and increased NK-cell immunity in patients with recurrent miscarriage.肾移植受者移植后期自然杀伤(NK)细胞免疫功能降低,而复发性流产患者的NK细胞免疫功能增强。
PLoS One. 2017 Oct 17;12(10):e0186349. doi: 10.1371/journal.pone.0186349. eCollection 2017.
3
Immune monitoring as prerequisite for transplantation tolerance trials.免疫监测作为移植耐受试验的前提条件。
Clin Exp Immunol. 2017 Aug;189(2):158-170. doi: 10.1111/cei.12988. Epub 2017 Jun 23.

本文引用的文献

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Soluble major histocompatibility complex class I chain-related antigen A level in chronic allograft dysfunction.
Iran J Kidney Dis. 2015 Mar;9(2):146-53.
2
Regulatory T cell subtypes and TGF-β1 gene expression in chronic allograft dysfunction.慢性移植肾失功中的调节性T细胞亚型及转化生长因子-β1基因表达
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Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions.班夫 2013 年会议报告:包含 C4d 阴性抗体介导的排斥反应和抗体相关的动脉病变。
Am J Transplant. 2014 Feb;14(2):272-83. doi: 10.1111/ajt.12590.
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The Peripheral NK Cell Repertoire after Kidney Transplantation is Modulated by Different Immunosuppressive Drugs.肾移植后外周 NK 细胞受体谱受不同免疫抑制药物的调节。
Front Immunol. 2013 Feb 28;4:46. doi: 10.3389/fimmu.2013.00046. eCollection 2013.
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Regulatory NK cells in autoimmune disease.自身免疫性疾病中的调节性自然杀伤细胞。
J Autoimmun. 2012 Sep;39(3):206-15. doi: 10.1016/j.jaut.2012.05.006. Epub 2012 Jun 15.
6
KIR and HLA-C interactions promote differential dendritic cell maturation and is a major determinant of graft failure following kidney transplantation.KIR 和 HLA-C 的相互作用促进了树突状细胞的成熟分化,是肾移植后移植物失功的主要决定因素。
PLoS One. 2011;6(8):e23631. doi: 10.1371/journal.pone.0023631. Epub 2011 Aug 31.
7
Renal transplant immunosuppression impairs natural killer cell function in vitro and in vivo.肾移植免疫抑制体外和体内损害自然杀伤细胞功能。
PLoS One. 2010 Oct 12;5(10):e13294. doi: 10.1371/journal.pone.0013294.
8
NK cells: elusive participants in transplantation immunity and tolerance.自然杀伤细胞:移植免疫和耐受中的难以捉摸的参与者。
Curr Opin Immunol. 2010 Oct;22(5):649-54. doi: 10.1016/j.coi.2010.09.005. Epub 2010 Oct 15.
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The molecular phenotype of kidney transplants.肾脏移植的分子表型。
Am J Transplant. 2010 Oct;10(10):2215-22. doi: 10.1111/j.1600-6143.2010.03267.x.
10
NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibody-mediated rejection.来自具有供体特异性抗体的患者的肾活检中的 NK 细胞转录本和 NK 细胞:NK 细胞参与抗体介导的排斥反应的证据。
Am J Transplant. 2010 Aug;10(8):1812-22. doi: 10.1111/j.1600-6143.2010.03201.x.