Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study

Autor: Shelley A. Hall, J. Yee, Sean Pinney, Robert Woodward, Gregory A. Ewald, D. Hiller, Andrew Kao, Jon A. Kobashigawa, Manreet Kanwar, Jignesh Patel, Kiran K. Khush, R.A. Alharethi, Peter Berman, Eugene C. DePasquale
Rok vydání: 2019
Předmět:
Graft Rejection
Male
030230 surgery
Gastroenterology
Postoperative Complications
0302 clinical medicine
Isoantibodies
Risk Factors
T-Lymphocyte Subsets
Immunology and Allergy
Pharmacology (medical)
Prospective Studies
Stage (cooking)
heart transplantation/cardiology
education.field_of_study
medicine.diagnostic_test
Graft Survival
Venous blood
Clinical Science
Middle Aged
Reference Standards
Prognosis
Tissue Donors
heart (allograft) function/dysfunction
Cell-free fetal DNA
Cohort
biomarker
Biomarker (medicine)
Original Article
Female
Cell-Free Nucleic Acids
Adult
medicine.medical_specialty
Population
Single-nucleotide polymorphism
clinical research/practice
Polymorphism
Single Nucleotide
03 medical and health sciences
Internal medicine
Biopsy
medicine
Humans
education
Aged
Transplantation
business.industry
Case-Control Studies
Heart Transplantation
ORIGINAL ARTICLES
business
Biomarkers
Follow-Up Studies
Zdroj: American Journal of Transplantation
ISSN: 1600-6135
Popis: Standardized donor‐derived cell‐free DNA (dd‐cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd‐cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single‐center cohort of 33 patients at high risk for antibody‐mediated rejection (AMR). Plasma dd‐cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd‐cfDNA levels were correlated to paired events of biopsy‐based diagnosis of rejection. The median dd‐cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd‐cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd‐cfDNA levels were elevated 3‐fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd‐cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd‐cfDNA assay.
A large multicenter study in a broad heart transplant surveillance population demonstrates the ability of standardized donor‐ derived cell‐free DNA testing to identify both T cell–mediated and antibody‐mediated acute rejection with a high negative predictive value.
Databáze: OpenAIRE
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