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Background: Donor-derived cell-free DNA (dd-cfDNA) testing is an emerging screening modality for noninvasive detection of acute rejection (AR). This study compared the testing accuracy for AR of two commercially available dd-cfDNA and gene-expression profiling (GEP) testing in heart transplant (HTx) recipients.
Methods: This is a retrospective, observational study of HTx only patients who underwent standard and expanded single nucleotide polymorphism (SNP) dd-cfDNA between October 2020 to January 2022. Comparison with GEP was also performed. Assays were compared for correlation, accurate classification, and prediction for AR.
Results: A total of 428 samples from 112 unique HTx patients were used for the study. A positive standard SNP correlated with the expanded SNP assay (p < .001). Both standard and expanded SNP tests showed low sensitivity (39%, p = 1.0) but high specificity (82% and 84%, p = 1.0) for AR. GEP did not improve sensitivity and showed worse specificity (p < .001) compared to standard dd-cfDNA.
Conclusion: We found no significant difference between standard and expanded SNP assays in detecting AR. We show improved specificity without change in sensitivity using dd-cfDNA in place of GEP testing. Prospective controlled studies to address how to best implement dd-cfDNA testing into clinical practice are needed.
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http://dx.doi.org/10.1111/ctr.14984 | DOI Listing |
Clin Transplant Res
September 2025
Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Donor-derived cell-free DNA (dd-cfDNA) has emerged as a valuable noninvasive biomarker for detecting allograft injury in solid organ transplantation. It is released into the bloodstream from the transplanted organ as a result of cell injury and immune activation, with baseline levels influenced by organ type, tissue turnover, and posttransplant physiological changes. Several analytical platforms are available, including quantitative polymerase chain reaction (PCR), digital droplet PCR, and next-generation sequencing, each differing in sensitivity, throughput, and reporting format.
View Article and Find Full Text PDFJ Hematol
August 2025
Department of Physiology and Pharmacology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX, USA.
Cell-free DNA (cfDNA) consists of fragmented nuclear and mitochondrial DNA circulating in the bloodstream, primarily originating from hematopoietic cells. While cfDNA analysis has transformed diagnostic medicine, its presence in transfused blood products introduces emerging clinical concerns. Donor-derived cfDNA may persist in transfusion recipients and contribute to transfusion-associated microchimerism, defined as the long-term presence of donor genetic material in recipient tissues or circulation.
View Article and Find Full Text PDFFront Transplant
August 2025
Department of Cardiovascular Disease, Inova Schar Heart and Vascular, Falls Church, VA, United States.
Despite significant advances in organ preservation, surgical techniques, and immunosuppressive regimens, rejection continues to pose a major challenge in the care of heart transplant patients. Endomyocardial biopsy (EMB) remains the gold standard test for surveillance and diagnosis of rejection, but is limited by its invasiveness, interobserver variability, procedural risk, and cost thus prompting the widespread use of non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA). Due to its high negative predictive value, dd-cfDNA is often routinely used for surveillance of asymptomatic patients.
View Article and Find Full Text PDFInt J Immunogenet
August 2025
Transplant Laboratory, University Hospitals of Leicester, Leicester, UK.
IgA nephropathy (IgAN) is one of the most prevalent glomerulonephropathies and commonly leads to kidney failure. The recurrence of IgAN following transplantation remains a significant concern. Currently, detecting IgAN recurrence requires a kidney biopsy, highlighting the need for non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) to aid in early detection.
View Article and Find Full Text PDFPediatr Transplant
September 2025
University of Michigan, Ann Arbor, Michigan, USA.
Background: Antibody-mediated rejection (AMR) remains a significant complication following heart transplantation, contributing to graft dysfunction and reduced survival. Donor-derived cell-free DNA (dd-cfDNA) is emerging as a non-invasive biomarker for detecting and monitoring graft injury, correlating with episodes of rejection and response to treatment. Daratumumab, an anti-CD38 monoclonal antibody targeting plasma cells, has shown promise in treating AMR.
View Article and Find Full Text PDF