Lack of Association Between Donor-Derived Cell-Free DNA and Cardiac Allograft Vasculopathy

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2024-07-26 DOI:10.1111/ctr.15416

Rami Alharethi, Stacey Knight, Helen I. Luikart, Theresa Wolf-Doty, Daniel L. Bride, Daniel. T. Kim, Kiran K. Khush

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引用次数: 0

Abstract

Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT). We evaluated donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker of CAV development after HT.

The INSPIRE registry at the Intermountain Medical Center was queried for stored plasma samples from HT patients with and without CAV. At Stanford University, HT patients with CAV (cases) and without CAV (controls) were enrolled prospectively, and blood samples were collected. All the samples were analyzed for dd-cfDNA using the AlloSure assay (CareDx, Inc.). CAV was defined per the ISHLT 2010 standardized classification system. Univariate associations between patient demographics and clinical characteristics and their CAV grade were tested using chi-square and Wilcoxon rank sum tests. Associations between their dd-cfDNA levels and CAV grades were examined using a nonparametric Kruskal–Wallis test.

A total of 69 pts were included, and 101 samples were analyzed for dd-cfDNA. The mean age at sample collection was 58.6 ± 13.7 years; 66.7% of the patients were male, and 81% were White. CAV 0, 1, 2, and 3 were present in 37.6%, 22.8%, 22.8%, and 16.8% of included samples, respectively. The median dd-cfDNA level was 0.13% (0.06, 0.33). The median dd-cfDNA level was not significantly different between CAV (−) and CAV (+): 0.09% (0.05%–0.32%) and 0.15% (0.07%–0.33%), respectively, p = 0.25 and with similar results across all CAV grades.

In our study, dd-cfDNA levels did not correlate with the presence of CAV and did not differ across CAV grades. As such, dd-cfDNA does not appear to be a reliable noninvasive biomarker for CAV surveillance.

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捐献者来源的细胞游离 DNA 与心脏移植血管病变之间缺乏关联。

心脏移植物血管病变（CAV）是心脏移植（HT）后死亡的主要原因。我们评估了供体来源的无细胞 DNA（dd-cfDNA）作为心脏移植后 CAV 发生的非侵入性生物标志物的作用。我们在山间医疗中心的 INSPIRE 登记处查询了患有和不患有 CAV 的 HT 患者的血浆样本。斯坦福大学对患有 CAV 的 HT 患者（病例）和未患有 CAV 的 HT 患者（对照）进行了前瞻性登记，并采集了血液样本。使用 AlloSure 分析法（CareDx, Inc.）CAV 根据 ISHLT 2010 标准化分类系统进行定义。采用秩方检验和 Wilcoxon 秩和检验对患者人口统计学特征和临床特征与 CAV 分级之间的单变量关系进行了检验。使用非参数 Kruskal-Wallis 检验法检验了 dd-cfDNA 水平与 CAV 分级之间的关系。共纳入 69 名患者，对 101 份样本进行了 dd-cfDNA 分析。样本采集时的平均年龄为 58.6 ± 13.7 岁；66.7% 的患者为男性，81% 为白人。37.6%、22.8%、22.8% 和 16.8% 的样本存在 CAV 0、1、2 和 3。dd-cfDNA 水平的中位数为 0.13% (0.06, 0.33)。中位 dd-cfDNA 水平在 CAV (-) 和 CAV (+) 之间无显著差异：分别为 0.09% (0.05%-0.32%) 和 0.15% (0.07%-0.33%)，p = 0.25，所有 CAV 等级的结果相似。在我们的研究中，dd-cfDNA水平与CAV的存在并无相关性，在不同CAV分级中也无差异。因此，dd-cfDNA 似乎不是监测 CAV 的可靠无创生物标志物。

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

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.