Rami Alharethi, Stacey Knight, Helen I. Luikart, Theresa Wolf-Doty, Daniel L. Bride, Daniel. T. Kim, Kiran K. Khush
{"title":"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。","authors":"Rami Alharethi, Stacey Knight, Helen I. Luikart, Theresa Wolf-Doty, Daniel L. Bride, Daniel. T. Kim, Kiran K. Khush","doi":"10.1111/ctr.15416","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>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.</p>\n <p>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.</p>\n <p>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, <i>p</i> = 0.25 and with similar results across all CAV grades.</p>\n <p>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.</p>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 7","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lack of Association Between Donor-Derived Cell-Free DNA and Cardiac Allograft Vasculopathy\",\"authors\":\"Rami Alharethi, Stacey Knight, Helen I. Luikart, Theresa Wolf-Doty, Daniel L. Bride, Daniel. T. Kim, Kiran K. Khush\",\"doi\":\"10.1111/ctr.15416\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>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.</p>\\n <p>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.</p>\\n <p>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, <i>p</i> = 0.25 and with similar results across all CAV grades.</p>\\n <p>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.</p>\\n </div>\",\"PeriodicalId\":10467,\"journal\":{\"name\":\"Clinical Transplantation\",\"volume\":\"38 7\",\"pages\":\"\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-07-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Transplantation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/ctr.15416\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Transplantation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/ctr.15416","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SURGERY","Score":null,"Total":0}
Lack of Association Between Donor-Derived Cell-Free DNA and Cardiac Allograft Vasculopathy
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.
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.
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