切换至 "中华医学电子期刊资源库"

中华移植杂志(电子版) ›› 2020, Vol. 14 ›› Issue (04) : 258 -262. doi: 10.3877/cma.j.issn.1674-3903.2020.04.015

所属专题: 文献

综述

细胞游离DNA监测在器官移植中的应用前景
钱佳俊1, 郭宏骞1,()   
  1. 1. 210008 南京鼓楼医院泌尿外科
  • 收稿日期:2019-10-22 出版日期:2020-08-25
  • 通信作者: 郭宏骞
  • 基金资助:
    江苏省"科教兴卫工程"医学重点学科(实验室)建设计划(ZDXKB2016014)

Application prospect of cell-free DNA monitoring in organ transplantation

Jiajun Qian1, Hongqian Guo1,()   

  1. 1. Urology Surgery, Nanjing Drum Tower Hospital, Nanjing 210008, China
  • Received:2019-10-22 Published:2020-08-25
  • Corresponding author: Hongqian Guo
  • About author:
    Corresponding author: Guo Hongqian, Email:
引用本文:

钱佳俊, 郭宏骞. 细胞游离DNA监测在器官移植中的应用前景[J]. 中华移植杂志(电子版), 2020, 14(04): 258-262.

Jiajun Qian, Hongqian Guo. Application prospect of cell-free DNA monitoring in organ transplantation[J]. Chinese Journal of Transplantation(Electronic Edition), 2020, 14(04): 258-262.

器官移植术后移植物排斥反应与损伤的监测一直未能得到很好的解决。细胞游离DNA(cfDNA)是一种可以在血液、尿液等体液中检测到的片段化、降解DNA。移植术后发生排斥反应时体液中cfDNA特异性升高,甚至在穿刺活检病理确诊排斥反应前数周,该指标已显著升高。有研究表明,供者来源细胞游离DNA(dd-cfDNA)水平与移植物损伤的严重程度和敏感度成正比,可能会成为移植术后检测移植物损伤或急性排斥反应的无创性动态指标。本文对cfDNA在器官移植监测中的研究进展作一综述。

Postoperative monitoring of allograft rejection and injury in organ transplant recipients has not been effectively resolved. Cell-free DNA (cfDNA) is a fragmented and degraded DNA that can be detected in blood, urine and other body fluids. Its content in body fluids increases specifically when rejection occures or even a few weeks before the pathological diagnosis of rejection by biopsy. Donor-derived cell-free DNA (dd-cfDNA) may become a noninvasive and dynamic indicator for detecting allograft damage or acute rejection after surgery, because dd-cfDNA levels are proportional to the severity and sensitivity of injury. Studies have shown that dd-cfDNA is proportional to the severity and sensitivity of the injury. This article will review the progress of cfDNA monitoring in organ transplantation.

1
Beck J, Oellerich M, Schulz U, et al. Donor-derived cell-free DNA is a novel universal biomarker for allograft rejection in solid organ transplantation[J]. Transplant Proc, 2015,47(8): 2400-2403.
2
Smith JM, Weaver T, Skeans MA, et al. OPTN/SRTR 2018 Annual Data Report: Intestine[J]. Am J Transplant, 2020,20 Suppl s1: 300-339.
3
Valapour M, Lehr CJ, Skeans MA, et al. OPTN/SRTR 2018 Annual Data Report: Lung[J]. Am J Transplant, 2020,20 Suppl s1: 427-508.
4
Kwong A, Kim WR, Lake JR, et al. OPTN/SRTR 2018 Annual Data Report: Liver[J]. Am J Transplant, 2020,20 Suppl s1: 193-299.
5
Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2018 Annual Data Report: Kidney[J]. Am J Transplant, 2020,20 Suppl s1: 20-130.
6
Colvin M, Smith JM, Hadley N, et al. OPTN/SRTR 2018 Annual Data Report: Heart[J]. Am J Transplant, 2020,20 Suppl s1: 340-426.
7
Kandaswamy R, Stock PG, Gustafson SK, et al. OPTN/SRTR 2018 Annual Data Report: Pancreas[J]. Am J Transplant, 2020,20 Suppl s1: 131-192.
8
Whitlam JB, Ling Ling, Skene A, et al. Diagnostic application of kidney allograft-derived absolute cell-free DNA levels during transplant dysfunction[J]. Am J Transplant, 2019,19(4): 1037-1049.
9
Zheng YW, Chan KC, Sun H, et al. Nonhematopoietically derived DNA is shorter than hematopoietically derived DNA in plasma: a transplantation model[J]. Clin Chem, 2012,58(3): 549-558.
10
Lui YY, Chik KW, Chiu RW, et al. Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation[J]. Clin Chem, 2002,48(3): 421-427.
11
Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients[J]. Nat Rev Cancer, 2011,11(6): 426-437.
12
Celec P, Vlková B, Lauková,et al. Cell-free DNA: the role in pathophysiology and as a biomarker in kidney diseases[J]. Expert Rev Mol Med, 2018,20: e1.
13
Yu SC, Lee SW, Jiang P, et al. High-resolution profiling of fetal DNA clearance from maternal plasma by massively parallel sequencing[J]. Clin Chem, 2013,59 (8): 1228-1237.
14
Shen J, Zhou Y, Chen Y, et al. Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study[J]. Transpl Int, 2019,32(2): 184-192.
15
Sigdel TK, Vitalone MJ, Tran TQ, et al. A rapid noninvasive assay for the detection of renal transplant injury[J]. Transplantation, 2013,96(1): 97-101.
16
Beck J, Bierau S, Balzer S, et al. Digital droplet PCR for rapid quantification of donor DNA in the circulation of transplant recipients as a potential universal biomarker of graft injury[J]. Clin Chem, 2013,59(12): 1732-1741.
17
Gielis EM, Beirnaert C, Dendooven A, et al. Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay[J]. PLoS One, 2018,13(12): e0208207.
18
De Vlaminck I, Martin L, Kertesz M, et al. Noninvasive monitoring of infection and rejection after lung transplantation[J]. Proc Natl Acad Sci U S A, 2015,112(43): 13336-13341.
19
Schütz E, Blum A, Beck J, et al. Graft-derived cell-free DNA - a promising rejection marker in liver transplantation - results from a prospective multicenter trial[J]. Clin Chem, 2016,62(10): S34.
20
Bloom RD, Bromberg JS, Poggio ED, et al. Cell-free DNA and active rejection in kidney allografts[J]. J Am Soc Nephrol, 2017,28(7): 2221-2232.
21
Sigdel TK, Archila FA, Constantin T,et al. Optimizing detection of kidney transplant injury by assessment of donor-derived cell-free DNA via massively multiplex PCR[J]. J Clin Med, 2018,8(1): 19.
22
Huang E, Sethi S, Peng A, et al. Early clinical experience using donor-derived cell-free DNA to detect rejection in kidney transplant recipients[J]. Am J Transplant, 2019,19(6): 1663-1670.
23
Macher HC, Suárez-Artacho G, Guerrero JM, et al. Monitoring of transplanted liver health by quantification of organ-specific genomic marker in circulating DNA from receptor[J]. PLoS One, 2014, 9: e113987.
24
Schütz E, Fischer A, Beck J, et al. Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: a prospective, observational, multicenter cohort study[J]. PLoS Med, 2017,14(4): e1002286.
25
von Meijenfeldt FA, Burlage LC, Bos S, et al. Elevated plasma levels of cell-free DNA during liver transplantation are associated with activation of coagulation[J]. Liver Transplant, 2018,24(12): 1716-1725.
26
Duque-Afonso J, Waterhouse M, Pfeifer D, et al. Cell-free DNA characteristics and chimerism analysis in patients after allogeneic cell transplantation[J]. Clin Biochem, 2018,52: 137-141.
27
Prakash K, Aggarwal S, Bhardwaj S, et al. Serial perioperative cell-free DNA levels in donors and recipients undergoing living donor liver transplantation[J]. Acta Anaesthesiol Scand, 2017,61(9): 1084-1094.
28
Snyder TM, Khush KK, Valantine HA, et al. Universal noninvasive detection of solid organ transplant rejection[J]. Proc Natl Acad Sci U S A, 2011,108(15): 6229-6234.
29
De Vlaminck I, Valantine HA, Snyder TM, et al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection[J]. Sci Transl Med, 2014,6(241): 241ra77.
30
Agbor-Enoh S, Tunc I, De Vlaminck I, et al. Applying rigor and reproducibility standards to assay donor-derived cell-free DNA as a non-invasive method of detection of acute rejection and graft injury after heart transplantation[J]. J Heart Lung Transplant, 2017,36(9): 1004-1012.
31
Tanaka S, Sugimoto S, Kurosaki T, et al. Donor-derived cell-free DNA is associated with acute rejection and decreased oxygenation in primary graft dysfunction after living donorlobar lung transplantation[J]. Sci Rep, 2018,8(1): 15366.
32
Gala-Lopez BL, Neiman D, Kin T, et al. Beta cell death by cell-free DNA and outcome after clinical islet transplantation[J]. Transplantation, 2018,102(6): 978-985.
33
García Moreira V, Prieto García B, Baltar Martin JM, et al. Cell-free DNA as a noninvasive acute rejection marker in renal transplantation[J]. Clin Chem, 2009,55(11): 1958-1966.
34
Oellerich M, Shipkova M, Asendorf T, et al. Absolute quantification of donor-derived cell-free DNA as a marker of rejection and graft injury in kidney transplantation: results from a prospective observational study[J]. Am J Transplant, 2019,19(11): 3087-3099.
35
Oellerich M, Schutz E, Kanzow P, et al. Use of graft-derived cellfree DNA as an organ integrity biomarker to reexamine effective tacrolimus trough concentrations after liver transplantation[J]. Ther Drug Monit, 2014,36(2): 136-140.
36
Londoño MC, Danger R, Giral M, et al. A need for biomarkers of operational tolerance in liver and kidney transplantation[J]. Am J Transplant, 2012,12(6): 1370-1377.
37
Gielis EM, Ledeganck KJ, De Winter BY, et al. Cell-free DNA: an upcoming biomarker in transplantation[J]. Am J Transplant, 2015,15(10): 2541-2551.
[1] 中国肝移植注册中心, 国家肝脏移植质控中心, 国家人体捐献器官获取质控中心, 国家骨科与运动康复临床医学研究中心, 中国医师协会器官移植医师分会移植器官质量控制专业委员会中国医院协会器官获取与分配工作委员会, 国家创伤医学中心器官保护专业委员会. 中国移植器官保护专家共识(2022版)[J]. 中华普通外科学文献(电子版), 2022, 16(04): 241-254.
[2] 江文诗, 何湘湘. 全球及我国器官捐献发展特征分析与学科建设[J]. 中华移植杂志(电子版), 2023, 17(05): 280-286.
[3] 中华医学会器官移植学分会, 中国医师协会器官移植医师分会, 上海医药行业协会. 中国肝、肾移植受者霉酚酸类药物应用专家共识(2023版)[J]. 中华移植杂志(电子版), 2023, 17(05): 257-272.
[4] 巨春蓉, 何建行, 钟南山. 咪唑立宾在器官移植领域的应用及展望[J]. 中华移植杂志(电子版), 2023, 17(04): 227-231.
[5] 中国康复医学会器官移植康复专业委员会. 成人实体器官移植后糖尿病管理专家共识[J]. 中华移植杂志(电子版), 2023, 17(04): 205-220.
[6] 艾紫叶, 李玲, 何重香, 黄伟, 叶啟发. 猪器官异种移植研究进展[J]. 中华移植杂志(电子版), 2023, 17(03): 186-191.
[7] 杨锦然, 李新长, 何小平, 傅俊, 龙成美, 陈志铭. 不破坏膈肌式肝肾联合获取术总结分析[J]. 中华移植杂志(电子版), 2023, 17(03): 146-151.
[8] 刘剑戎, 范明明, 郭煜. 器官捐献者转介时的临床特征分析[J]. 中华移植杂志(电子版), 2023, 17(03): 129-133.
[9] 陈琦, 郭嘉瑜, 陈忠宝, 马枭雄, 王天宇, 邹寄林, 张龙, 蔡治涛, 邱涛, 周江桥. 心肾联合移植三例[J]. 中华移植杂志(电子版), 2023, 17(02): 124-127.
[10] 陈琦, 郭嘉瑜, 陈忠宝, 马枭雄, 王天宇, 邹寄林, 张龙, 蔡治涛, 邱涛, 周江桥. 新型冠状病毒感染流行下我国器官捐献者筛选规则是否应时而变?[J]. 中华移植杂志(电子版), 2023, 17(02): 82-88.
[11] 国家传染病医学中心, 中华医学会器官移植学分会, 中国康复医学会器官移植康复专业委员会, 中国器官移植发展基金会器官移植受者健康管理专项基金. 实体器官移植受者新型冠状病毒感染诊疗专家共识(2023年版)[J]. 中华移植杂志(电子版), 2023, 17(02): 65-81.
[12] 中国器官移植发展基金会器官移植受者健康管理专家委员会. 器官移植受者新型冠状病毒感染防治策略与健康管理中国专家指导意见(第一版)[J]. 中华移植杂志(电子版), 2023, 17(01): 1-12.
[13] 刘路浩, 李国君, 熊韫祎, 陈荣鑫, 尹威, 张磊, 李光辉, 方佳丽, 马俊杰, 陈正. 胰肾联合移植供者来源细胞游离DNA水平变化与术后急性排斥反应的相关研究[J]. 中华移植杂志(电子版), 2022, 16(06): 353-358.
[14] 中国医师协会器官移植医师分会, 中华医学会器官移植学分会. 中国实体器官移植手术部位感染管理专家共识(2022版)[J]. 中华移植杂志(电子版), 2022, 16(03): 129-139.
[15] 贺海燕, 谢文照. 公民自愿捐献器官的家庭文化模式初步探讨[J]. 中华临床医师杂志(电子版), 2022, 16(12): 1269-1275.
阅读次数
全文


摘要