Division of Nephrology, Department of Internal Medicine, University of New Mexico, Albuquerque, NM.
Division of Nephrology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA.
Transplantation. 2021 Jun 1;105(6):1203-1211. doi: 10.1097/TP.0000000000003651.
The last few years have seen an explosion in clinical research focusing on the use of donor-derived cell-free DNA (dd-cfDNA) in solid-organ transplants (SOT). Although most of the literature published so far focuses on kidney transplants, there are several recent as well as ongoing research studies on heart, lung, pancreas, and liver transplants. Though initially studied as a noninvasive means of identifying subclinical or acute rejection in SOT, it is rapidly becoming clear that instead of being a specific marker for allograft rejection, dd-cfDNA is more appropriately described as a marker of severe injury, although the most common cause of this injury is allograft rejection. Multiple studies in kidney transplants have shown that although sensitivity for the diagnosis of antibody-mediated rejection is excellent, it is less so for T-cell-mediated rejection. It is possible that combining dd-cfDNA with other novel urine- or blood-based biomarkers may increase the sensitivity for the diagnosis of rejection. Irrespective of the cause, though, elevated dd-cfDNA seems to portend adverse allograft prognosis and formation of de novo donor-specific antibody. Although current data do not lend themselves to a clear conclusion, ongoing studies may reveal the utility of serial surveillance for the management of SOT as following levels of dd-cfDNA over time may provide windows of opportunity to intervene early and before irreversible allograft injury. Finally, cost-effectiveness studies will be needed to guide the ideal incorporation of dd-cfDNA into routine clinical practice.
过去几年，针对供体来源无细胞游离 DNA（dd-cfDNA）在实体器官移植（SOT）中的应用的临床研究呈爆炸式增长。尽管迄今为止发表的大多数文献都集中在肾移植上，但也有一些关于心脏、肺、胰腺和肝移植的近期和正在进行的研究。虽然最初研究它是作为一种非侵入性手段来识别 SOT 中的亚临床或急性排斥反应，但越来越明显的是，dd-cfDNA 不是同种异体移植排斥的特异性标志物，而是更恰当地描述为严重损伤的标志物，尽管这种损伤最常见的原因是同种异体移植排斥反应。多项肾移植研究表明，虽然 dd-cfDNA 对抗体介导排斥反应的诊断具有很好的敏感性，但对 T 细胞介导的排斥反应的敏感性较低。将 dd-cfDNA 与其他新型尿液或血液生物标志物结合使用，可能会提高排斥反应的诊断敏感性。尽管无论病因如何，升高的 dd-cfDNA 似乎预示着同种异体移植物预后不良和新的供体特异性抗体的形成。尽管目前的数据无法得出明确的结论，但正在进行的研究可能会揭示连续监测对 SOT 管理的效用，因为随着时间的推移检测 dd-cfDNA 的水平可能提供早期干预的机会，在不可逆的同种异体移植物损伤之前。最后，需要进行成本效益研究来指导将 dd-cfDNA 理想地纳入常规临床实践。
