Application prospect of cell-free DNA monitoring in organ transplantation

doi:10.3877/cma.j.issn.1674-3903.2020.04.015

Abstract

Abstract:

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.

Key words: Cell-free DNA, Organ transplantation, Early monitoring, Dynamic indicator

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.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhyzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3903.2020.04.015

https://zhyzzz.cma-cmc.com.cn/EN/Y2020/V14/I04/258

References 37

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]	China Liver Transplant Registry, National Center for Healthcare Quality Management in Liver Transplant, National Quality Control Center for Human Donated Organ Procurement, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Committee on Transplant Organ Quality Control, Branch of Organ Transplant Physicians of Chinese Medical Doctor Association, Organ Procurement and Allocation Working Committee of the China Hospital Association, National Trauma Medical Center Organ Protection Committee. Chinese expert consensus on organ protection of transplantation (2022 edition) [J]. Chinese Archives of General Surgery(Electronic Edition), 2022, 16(04): 241-254.
[2]	Wenshi Jiang, Xiangxiang He. Analysis of the development characteristics and discipline construction of organ donation globally and in China [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(05): 280-286.
[3]	Branch of Organ Transplant of Chinese Medical Association, Branch of Organ Transplant Physicians of Chinese Medical Doctor Association, Shanghai Pharmaceutical Profession Association. Expert Consensus on the Use of Mycophenolic Acid in Chinese Liver and Kidney Transplant Recipients (2023 edition) [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(05): 257-272.
[4]	Organ Transplantation and Rehabilitation Committee of Chinese Medical Association of Rehabilitation. Expert consensus on diabetes mellitus after solid organ transplantation in adults [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(04): 205-220.
[5]	Chunrong Ju, Jianxing He, Nanshan Zhong. The application and future prospects of mizoribine in the field of organ transplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(04): 227-231.
[6]	Jinran Yang, Xinchang Li, Xiaoping He, Jun Fu, Chengmei Long, Zhiming Chen. Summary and analysis of combined liver and kidney procurement technology without destruction of diaphragm [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(03): 146-151.
[7]	Jianrong Liu, Mingming Fan, Yu Guo. Analysis of clinical characteristics of organ donors at referral [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(03): 129-133.
[8]	Qi Chen, Jiayu Guo, Zhongbao Chen, Xiaoxiong Ma, Tianyu Wang, Jilin Zou, Long Zhang, Zhitao Cai, Tao Qiu, Jiangqiao Zhou. Combined heart and kidney transplantation: a report of 3 cases [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(02): 124-127.
[9]	Qi Chen, Jiayu Guo, Zhongbao Chen, Xiaoxiong Ma, Tianyu Wang, Jilin Zou, Long Zhang, Zhitao Cai, Tao Qiu, Jiangqiao Zhou. Should our screening rules for organ donors be changed under the current COVID-19 pandemic? [J]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(02): 82-88.
[10]	Luhao Liu, Guojun Li, Yunyi Xiong, Rongxin Chen, Wei Yin, Lei Zhang, Guanghui Li, Jiali Fang, Junjie Ma, Zheng Chen. Predictive value of donor-derived cell-free DNA in simultaneous pancreas-kidney transplantation recipients with acute rejection [J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(06): 353-358.
[11]	Mingshi Ren, Rong Wang, Mingyan Wang, Liyue Zhang, Nan Cheng, Yuanbin Wu. The research progress in gene modification strategies and perioperative management of cardiac xenotransplantation [J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(03): 183-189.
[12]	Jinjiang Zhu, Ling Bai, Hua Wang, Guozhen Chen, Haiping Liu, Chenguang Ding. The application of blockchain technology in organ donation and transplantation after the death of citizens [J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(03): 165-167.
[13]	Chinese College of Transplant Doctors, Chinese Medical Doctor Association;, Chinese Society of Organ Transplantation, Chinese Medical Association. Chinese experts consensus on the management of surgical site infection in solid organ transplantation (2022 edition) [J]. Chinese Journal of Transplantation(Electronic Edition), 2022, 16(03): 129-139.
[14]	Jianrong Liu, Tianwei Xiong, Mi Zhou, Xvxia Wei, Yuling An, Xiaomeng Yi, Lijuan Li, Pinglan Lu, Mingming Fan, Ziyu Li, Yang Yang, Huimin Yi. Effect of donor management scheme on organ donation outcome [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(06): 589-593.
[15]	Haiyan He, Wenzhao Xie. Preliminary research on family cultural model of voluntary organ donation [J]. Chinese Journal of Clinicians(Electronic Edition), 2022, 16(12): 1269-1275.

Please choose a citation manager

Content to export