Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection.
Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection.
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DOI：
10.1126/scitranslmed.3007803
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发表时间：
2014-06-18
影响因子：
17.1
通讯作者：
Khush KK
中科院分区：
文献类型：
--
作者：
De Vlaminck I;Valantine HA;Snyder TM;Strehl C;Cohen G;Luikart H;Neff NF;Okamoto J;Bernstein D;Weisshaar D;Quake SR;Khush KK
监测同种异体移植物的健康是移植后治疗的重要组成部分。心内膜心肌活检是目前心脏移植物监测的金标准，但它是一种昂贵的侵入性手术。基于循环无细胞供体衍生DNA(CfdDNA)高通量筛查的通用、非侵入性诊断方法的原理最近在一个小型回顾队列中得到了证明。我们介绍了一项前瞻性队列研究(65名患者，565个样本)的结果，该研究测试了cfdDNA在测量心脏移植后急性排斥反应中的有效性。从血浆中提纯循环中的无细胞DNA，并进行测序(平均深度为1.2千兆碱基对)以量化cfdDNA的比例。通过与心内膜心肌活检结果的比较，我们证明cfdDNA能够诊断心脏移植后的急性排斥反应，其受试者工作特征曲线下的面积为0.83，敏感性和特异性与活检本身的内在性能相当。这种非侵入性基因组移植动力学方法是一种强大且信息丰富的方法，可用于常规监测同种异体移植物的健康状况，而不会招致侵入性活组织检查的风险、不适和费用。
Monitoring allograft health is an important component of posttransplant therapy. Endomyocardial biopsy is the current gold standard for cardiac allograft monitoring but is an expensive and invasive procedure. Proof of principle of a universal, noninvasive diagnostic method based on high-throughput screening of circulating cell-free donor-derived DNA (cfdDNA) was recently demonstrated in a small retrospective cohort. We present the results of a prospective cohort study (65 patients, 565 samples) that tested the utility of cfdDNA in measuring acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (mean depth, 1.2 giga–base pairs) to quantify the fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, we demonstrate that cfdDNA enables diagnosis of acute rejection after heart transplantation, with an area under the receiver operating characteristic curve of 0.83 and sensitivity and specificity that are comparable to the intrinsic performance of the biopsy itself. This noninvasive genome transplant dynamics approach is a powerful and informative method for routine monitoring of allograft health without incurring the risk, discomfort, and expense of an invasive biopsy.
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影响因子：
9.3
作者：
Beck, Julia;Bierau, Sarah;Schuetz, Ekkehard
通讯作者：
Schuetz, Ekkehard
影响因子：
8.8
作者：
Deng, MC;Eisen, HJ;Hunt, S
通讯作者：
Hunt, S
影响因子：
8.9
作者：
Stewart, S;Winters, GL;Billingham, ME
通讯作者：
Billingham, ME
影响因子：
64.5
作者：
De Vlaminck I;Khush KK;Strehl C;Kohli B;Luikart H;Neff NF;Okamoto J;Snyder TM;Cornfield DN;Nicolls MR;Weill D;Bernstein D;Valantine HA;Quake SR
通讯作者：
Quake SR
DOI：
10.1073/pnas.0808319105
发表时间：
2008-10-21
影响因子：
11.1
作者：
Fan, H. Christina;Blumenfeld, Yair J.;Quake, Stephen R.
通讯作者：
Quake, Stephen R.