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中华移植杂志(电子版)

中华移植杂志(电子版) ›› 2021, Vol. 15 ›› Issue (04) : 244 -249. doi: 10.3877/cma.j.issn.1674-3903.2021.04.012

综述

实体器官移植后移植物长期存活评估相关生物标志物研究进展
胡正斌1, 周鑫1,†(), 熊艳1, 范晓礼1, 范志鹏1, 叶啟发2   
  1. 1. 430071　武汉大学中南医院肝胆疾病研究院　武汉大学肝胆疾病研究院　武汉大学移植医学中心　国家人体捐献器官获取质量控制中心　移植医学技术湖北省重点实验室　湖北省天然高分子生物肝临床医学研究中心　湖北省天然高分子基医用材料构建工程技术研究中心
    2. 430071　武汉大学中南医院肝胆疾病研究院　武汉大学肝胆疾病研究院　武汉大学移植医学中心　国家人体捐献器官获取质量控制中心　移植医学技术湖北省重点实验室　湖北省天然高分子生物肝临床医学研究中心　湖北省天然高分子基医用材料构建工程技术研究中心；410013　长沙，中南大学湘雅三医院移植中心　卫生部移植医学工程技术研究中心
  • 收稿日期:2020-12-30 出版日期:2021-08-25
  • 通信作者: 周鑫
  • 基金资助:
    国家自然科学基金(81970548); 医学腾飞计划——"转化医学、医学+平台建设项目"（临床医学）(TFLC2018003); 武汉市科技计划项目(2019020701011485)

Research progress on biomarkers related to long-term graft survival evaluation after solid organ transplantation

Zhengbin Hu1, Xin Zhou1,†(), Yan Xiong1, Xiaoli Fan1, Zhipeng Fan1, Qifa Ye2   

  1. 1. Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, WuHan 430071, China
    2. Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, WuHan 430071, China; Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Transplantation center of Xiangya Third Hospital of Central South University, Changsha 410013, China
  • Received:2020-12-30 Published:2021-08-25
  • Corresponding author: Xin Zhou
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胡正斌, 周鑫, 熊艳, 范晓礼, 范志鹏, 叶啟发. 实体器官移植后移植物长期存活评估相关生物标志物研究进展[J]. 中华移植杂志(电子版), 2021, 15(04): 244-249.

Zhengbin Hu, Xin Zhou, Yan Xiong, Xiaoli Fan, Zhipeng Fan, Qifa Ye. Research progress on biomarkers related to long-term graft survival evaluation after solid organ transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2021, 15(04): 244-249.

随着器官移植手术技术的成熟，实体器官移植物长期存活逐渐成为移植术后的首要任务。实体器官移植后移植物功能丢失的主要原因是慢性移植物损伤，但其潜在机制尚不明确。移植物病理活检是用于诊断移植物功能状况的金标准，但因活检穿刺操作的侵入性以及取样的局限性，阻碍移植物功能状况的常规评估。因此，微损伤非侵入性样品(例如外周血或尿液)功能性监测，更利于实体器官移植术后移植物的管理。本文对实体器官移植中移植物长期存活的生物标志物研究进展作一综述。

关键词: 实体器官移植, 移植物功能丢失, 慢性移植物损伤, 长期存活, 生物标志物

With the maturity of organ transplantation technology, the long-term survival of solid organ grafts has gradually become the primary task after transplantation. The main cause of graft function loss after solid organ transplantation is chronic graft damage. However, its potential mechanism is not clear. Graft pathological biopsy is the gold standard for the diagnosis of graft function, but the routine evaluation of graft function is hindered by the invasiveness of biopsy puncture and the limitation of sampling. Therefore, functional monitoring of micro injury non-invasive samples (such as peripheral blood or urine) is more conducive to the management of grafts after solid organ transplantation. This paper will systematically review the literature on biomarkers of long-term graft survival in solid organ transplantation.

Key words: Solid organ transplantation, Loss of graft function, Chronic allograft damage, Long-term survival, Biomarkers
表1 实体器官移植后AR生物标志物
器官 检测样本 研究目的 生物标志物 参考文献
肾 血液(PBMC mRNA)、尿液(mRNA) 诊断AR的细胞毒性蛋白质 Fas配体、颗粒酶B、穿孔素 [17,21,22,23]
肾、肺、肝、心脏 血液(PBMC)、血清、BALF、尿液(mRNA、蛋白质) 供者/受者细胞因子表达预测/检测AR CXCR3、CXCL9、CXCL10 [24,25,26,27,28]
肾 组织活检、血液(PBMC, mRNA) 与AR相关的miRNA变化 miR-142-5p、miR-155、miR-223 [29,30,31,32]
肾 组织活检 抗体介导排斥反应的生物标志物(诊断/预测) CD38、内皮细胞基因 [33,34]
肾 组织活检、血清(蛋白质) 抗新型非HLA抗体(诊断/预测) AT1R-AA、MICA、Duffy、Kidd、Agrin [16,35,36,37,38]
肾、心脏 组织活检、血清(mRNA、蛋白质) 预测和诊断器官AR的整合蛋白质组学生物标志物 新型非HLA: PECAM-1 [13,39]
表2 器官移植后CAD生物标志物
器官 检测样本 研究目的 生物标志物 参考文献
肾 血液(mRNA)、组织活检(mRNA)、尿液(mRNA) 预测轻度/中度CAD和慢性抗体介导损伤的外周基因和蛋白质 TRIB1、CCL2 [50,56,57]
肾、心脏 血液(蛋白质)、组织活检(mRNA)、尿液(蛋白质) 间质纤维化、肾小管萎缩和抗纤维化靶标的早期外周血和尿液基因表达诊断 KIM-1、CTGF [46,47,53,54]
表3 器官移植后移植免疫耐受生物标志物
器官 检测样本 研究目的 生物标志物 参考文献
肾、肝 血液(PBMC、mRNA) 识别移植受者免疫排斥反应沉默的外周基因表达 KLRF1、SLAMF、FEZ1、CD160等343个基因 [58,59]
肾 血液(mRNA) 移植受者PBMC中B淋巴细胞相关基因特征的耐受性 B细胞特征(IGKV4-1、IGKV1D-13、IGLL1)、FOXP3/α-1，2-甘露糖苷酶的比例 [60,61]
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