Dana Dlouha, Sarka Chytilova, Jevgenija Vymetalova, Eva Rohlova, Marianna Lukasova, Sarka Novakova, Jaroslav Alois Hubacek
{"title":"增加供体来源的无细胞DNA作为心脏移植后抗体介导排斥反应早期检测的预测因子","authors":"Dana Dlouha, Sarka Chytilova, Jevgenija Vymetalova, Eva Rohlova, Marianna Lukasova, Sarka Novakova, Jaroslav Alois Hubacek","doi":"10.1111/ctr.70209","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Plasma circulating donor-derived cell-free DNA (ddcfDNA) can be used to noninvasively monitor acute rejection of heart transplants (HTx). This study utilized digital droplet PCR to analyze ddcfDNA concentrations (measured in copies per milliliter) and the fractional abundance (%ddcfDNA) to differentiate between donor and recipient DNA on the basis of single nucleotide polymorphism (SNP) homozygosity. Seventy-seven patients participated in a study, providing 300 plasma samples. Both markers, mean ddcfDNA (cp/mL) and %ddcfDNA, showed similar decreasing trends following the HTx, (<i>R</i><sup>2</sup> < 0.2; <i>p</i> < 0.001). Significantly higher levels of ddcfDNA (cp/mL) and %ddcfDNA were observed during episodes of acute rejection (AR) compared to non-rejection samples (<i>p</i> < 0.001). Additionally, antibody-mediated rejection (AMR) was associated with increased %ddcfDNA levels compared to non-rejection and to acute cellular rejection samples (<i>p</i> < 0.001 and <i>p</i> < 0.01). A logistic regression model identified %ddcfDNA as an early predictor of AMR risk 10–19 days post-heart transplant (odds ratio 158, <i>p</i> < 0.02). Performance analysis established an optimal %ddcfDNA threshold of 0.125% for AMR detection, correctly identifying all patients without subsequent AMR. These findings suggest that early %ddcfDNA measurements post-HTx can accurately identify individuals unlikely to develop AMR during the first posttransplant year.</p>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 6","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Increased Donor-Derived Cell-Free DNA as a Predictor for the Early Detection of Antibody-Mediated Rejection Following Heart Transplantation\",\"authors\":\"Dana Dlouha, Sarka Chytilova, Jevgenija Vymetalova, Eva Rohlova, Marianna Lukasova, Sarka Novakova, Jaroslav Alois Hubacek\",\"doi\":\"10.1111/ctr.70209\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Plasma circulating donor-derived cell-free DNA (ddcfDNA) can be used to noninvasively monitor acute rejection of heart transplants (HTx). This study utilized digital droplet PCR to analyze ddcfDNA concentrations (measured in copies per milliliter) and the fractional abundance (%ddcfDNA) to differentiate between donor and recipient DNA on the basis of single nucleotide polymorphism (SNP) homozygosity. Seventy-seven patients participated in a study, providing 300 plasma samples. Both markers, mean ddcfDNA (cp/mL) and %ddcfDNA, showed similar decreasing trends following the HTx, (<i>R</i><sup>2</sup> < 0.2; <i>p</i> < 0.001). Significantly higher levels of ddcfDNA (cp/mL) and %ddcfDNA were observed during episodes of acute rejection (AR) compared to non-rejection samples (<i>p</i> < 0.001). Additionally, antibody-mediated rejection (AMR) was associated with increased %ddcfDNA levels compared to non-rejection and to acute cellular rejection samples (<i>p</i> < 0.001 and <i>p</i> < 0.01). A logistic regression model identified %ddcfDNA as an early predictor of AMR risk 10–19 days post-heart transplant (odds ratio 158, <i>p</i> < 0.02). Performance analysis established an optimal %ddcfDNA threshold of 0.125% for AMR detection, correctly identifying all patients without subsequent AMR. These findings suggest that early %ddcfDNA measurements post-HTx can accurately identify individuals unlikely to develop AMR during the first posttransplant year.</p>\\n </div>\",\"PeriodicalId\":10467,\"journal\":{\"name\":\"Clinical Transplantation\",\"volume\":\"39 6\",\"pages\":\"\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-06-06\",\"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.70209\",\"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.70209","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SURGERY","Score":null,"Total":0}
Increased Donor-Derived Cell-Free DNA as a Predictor for the Early Detection of Antibody-Mediated Rejection Following Heart Transplantation
Plasma circulating donor-derived cell-free DNA (ddcfDNA) can be used to noninvasively monitor acute rejection of heart transplants (HTx). This study utilized digital droplet PCR to analyze ddcfDNA concentrations (measured in copies per milliliter) and the fractional abundance (%ddcfDNA) to differentiate between donor and recipient DNA on the basis of single nucleotide polymorphism (SNP) homozygosity. Seventy-seven patients participated in a study, providing 300 plasma samples. Both markers, mean ddcfDNA (cp/mL) and %ddcfDNA, showed similar decreasing trends following the HTx, (R2 < 0.2; p < 0.001). Significantly higher levels of ddcfDNA (cp/mL) and %ddcfDNA were observed during episodes of acute rejection (AR) compared to non-rejection samples (p < 0.001). Additionally, antibody-mediated rejection (AMR) was associated with increased %ddcfDNA levels compared to non-rejection and to acute cellular rejection samples (p < 0.001 and p < 0.01). A logistic regression model identified %ddcfDNA as an early predictor of AMR risk 10–19 days post-heart transplant (odds ratio 158, p < 0.02). Performance analysis established an optimal %ddcfDNA threshold of 0.125% for AMR detection, correctly identifying all patients without subsequent AMR. These findings suggest that early %ddcfDNA measurements post-HTx can accurately identify individuals unlikely to develop AMR during the first posttransplant year.
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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