Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-01 DOI:10.1111/petr.14708

Shriprasad R Deshpande, Steven D Zangwill, Marc E Richmond, Steven J Kindel, Jacob N Schroder, Nunzio Gaglianello, David P Bichell, Mark A Wigger, Kenneth R Knecht, Phillip T Thrush, William T Mahle, Paula E North, Pippa M Simpson, Liyun Zhang, Mahua Dasgupta, Aoy Tomita-Mitchell, Michael E Mitchell

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Abstract

Background: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection.

Methods: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance.

Results: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection.

Conclusion: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

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使用临床可用的检测方法评估小儿和成人心脏移植排斥反应中供体部分无细胞 DNA 的阈值。

研究背景该研究的目的是评估临床上可用的无细胞DNA（cfDNA）测定在一大批儿童和成人心脏移植受者中的性能，并评估特定切点在检测排斥反应方面的性能：观察性、非干预性、前瞻性研究招募了来自七个中心的儿童和成人心脏移植受者。活检相关血浆样本用于 cfDNA 测量。对预先确定的切点进行了分析性能测试：共有来自 160 名受试者的 487 份样本被用于分析。排斥样本[0.21%（IQR 0.12-0.69）]和健康样本[0.05%（IQR 0.01-0.14），p]的 df-cfDNA 值存在明显差异：该研究表明，与成人相比，儿科排斥反应患者的循环 df-cfDNA 水平更高，并支持儿科和成人患者临床使用的特定切点，总体表现可接受。

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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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.