PDF(Pubmed)
Abstract：
The routine use of donor-derived cell-free DNA (dd-cfDNA) assays to monitor graft damage in patients after kidney transplantation is being implemented in many transplant centers worldwide. The interpretation of the results can be complicated in the setting of multiple sequential kidney transplantations where accurate donor assignment of the detected dd-cfDNA can be methodologically challenging.
We investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations.
The assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%-0.6% and showed a fluctuation over time in patients where we analyzed sequential samples.
This is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making.
We investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations.
The assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%-0.6% and showed a fluctuation over time in patients where we analyzed sequential samples.
This is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making.
摘要：
■全世界许多移植中心正在实施常规使用供体来源的无细胞DNA（dd-cfDNA）测定法来监测肾移植后患者的移植物损伤。结果的解释在多个顺序肾移植的设置中可能是复杂的,其中检测到的dd-cfDNA的准确供体分配在方法上可能是具有挑战性的。
■我们研究了一种新的基于下一代测序（NGS）的dd-cfDNA分析的能力，以准确识别人工产生的样本以及临床样本中检测到的dd-cfDNA的来源来自31例接受过两次顺序肾脏移植的患者。
■该测定在我们的人工生成的嵌合样品实验中在临床上有意义的定量范围内定量和正确分配dd-cfDNA方面显示出高准确性。在我们的临床样本中，我们能够在20%的分析患者中检测到首次移植(无功能)移植物的dd-cfDNA.从第一次移植物中检测到的dd-cfDNA的量始终在0.1％-0.6％的范围内，并且在我们分析顺序样品的患者中显示出随时间的波动。
■这是有关使用dd-cfDNA测定法检测来自多个肾脏移植的dd-cfDNA的第一份报告。我们的数据表明，移植患者的临床相关部分具有来自第一个供体移植物的可检测dd-cfDNA，并且检测到的dd-cfDNA的量在可能影响临床决策的范围内。
■我们研究了一种新的基于下一代测序（NGS）的dd-cfDNA分析的能力，以准确识别人工产生的样本以及临床样本中检测到的dd-cfDNA的来源来自31例接受过两次顺序肾脏移植的患者。
■该测定在我们的人工生成的嵌合样品实验中在临床上有意义的定量范围内定量和正确分配dd-cfDNA方面显示出高准确性。在我们的临床样本中，我们能够在20%的分析患者中检测到首次移植(无功能)移植物的dd-cfDNA.从第一次移植物中检测到的dd-cfDNA的量始终在0.1％-0.6％的范围内，并且在我们分析顺序样品的患者中显示出随时间的波动。
■这是有关使用dd-cfDNA测定法检测来自多个肾脏移植的dd-cfDNA的第一份报告。我们的数据表明，移植患者的临床相关部分具有来自第一个供体移植物的可检测dd-cfDNA，并且检测到的dd-cfDNA的量在可能影响临床决策的范围内。
