Absolute Quantification of Donor-Derived Cell-Free DNA Following Pediatric and Adult Heart Transplantation.

Jens Böhmer,Håkan Wåhlander,Karin Tran-Lundmark,Michal Odermarsky,Maria Sjöborg Alpman,Julia Asp,Staffan Nilsson,Kristjan Karason,Sunnegårdh Jan,Anne Ricksten,Göran Dellgren
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Abstract

OBJECTIVE Traditional rejection surveillance after heart transplantation (HTx) is based on endomyocardial biopsies (EMB), which are invasive, expensive and associated with complications. Monitoring using cell-free DNA (cfDNA) is promising, but most studies report only on the donor fraction (DF) as the percentage of donor derived-cfDNA (dd-cfDNA) relative to total-cfDNA. We evaluated the performance of absolute as well as relative levels of dd-cfDNA to detect rejection. METHODS HTx patients were prospectively enrolled in a multicenter study, and blood samples collected concurrently with EMB. Dd-cfDNA was quantified using droplet digital PCR (ddPCR). Rejection was defined by EMB-results and compared to non-rejection EMB. Patients with symptomatic rejection were studied as a subgroup and test performance was determined using ROC-analysis. RESULTS We included 94 patients (70 adults and 24 children) undergoing rejection surveillance during the first year after HTx, which resulted in 1007 EMB and blood samples. In 19 patients, there were 32 rejection episodes > 14 days past HTx, with 15 of them being symptomatic. In ROC analysis, dd-cfDNA and DF could discriminate quiescence from rejection with an AUC of 0.68 and 0.65, respectively. Dd-cDNA at a threshold of 25 copies/ml showed an AUC of 0.87 to detect symptomatic rejection, significantly better than DF (AUC of 0.75). CONCLUSIONS dd-cfDNA found good discrimination between cardiac recipients with and without rejection. Absolute quantification of dd-cfDNA with ddPCR is a fast and effective method to monitor graft health. Analyzing absolute dd-cfDNA levels helps identify other factors, besides rejection, that may influence cfDNA levels, potentially reducing the need for EMB.
儿童和成人心脏移植后供体来源无细胞DNA的绝对定量。
目的传统的心脏移植术后排斥反应监测是基于心内膜肌活检(EMB),这是一种侵入性的、昂贵的、有并发症的方法。使用游离DNA (cfDNA)进行监测是有希望的,但大多数研究只报道了供体部分(DF),即供体衍生cfDNA (dd-cfDNA)相对于总cfDNA的百分比。我们评估了绝对和相对水平的dd-cfDNA检测排斥反应的性能。方法将shtx患者前瞻性纳入一项多中心研究,同时采集EMB的血液样本。采用液滴数字PCR (ddPCR)对Dd-cfDNA进行定量。排斥反应由EMB结果定义,并与非排斥反应的EMB进行比较。出现症状性排斥反应的患者作为一个亚组进行研究,采用roc分析确定试验表现。结果94例患者(70名成人和24名儿童)在HTx治疗后的第一年接受了排斥反应监测,结果为1007份EMB和血液样本。在19例患者中,HTx术后14天发生32次排斥反应,其中15例有症状。在ROC分析中,dd-cfDNA和DF可以区分静止和排斥反应,AUC分别为0.68和0.65。在阈值为25拷贝/ml时,Dd-cDNA检测排斥反应的AUC为0.87,显著优于DF (AUC为0.75)。结论sd - cfdna对有排斥反应和无排斥反应的心脏受者具有良好的鉴别能力。ddPCR绝对定量检测dd-cfDNA是一种快速有效的移植物健康监测方法。分析绝对dd-cfDNA水平有助于确定除排异反应外可能影响cfDNA水平的其他因素,从而潜在地减少对EMB的需求。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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