Donor-derived cell-free DNA accurately detects acute rejection in lung transplant patients, a multicenter cohort study.

Autor:	Jang MK; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland., Tunc I; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland., Berry GJ; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Stanford University School of Medicine, Palo Alto, California., Marboe C; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Department of Pathology, New York Presbyterian University Hospital of Cornell and Columbia, New York, New York., Kong H; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland., Keller MB; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, 1830 East Monument Street, Baltimore, Maryland., Shah PD; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, 1830 East Monument Street, Baltimore, Maryland., Timofte I; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; University of Maryland Medical Center, Baltimore, Maryland., Brown AW; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Inova Fairfax Hospital, Fairfax, Virginia., Ponor IL; Department of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland., Mutebi C; Immunogenetics Core Laboratory, Johns Hopkins Hospital, Baltimore, Maryland., Philogene MC; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; National Cancer Institute, Rockville, Maryland., Yu K; National Cancer Institute, Rockville, Maryland., Iacono A; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; University of Maryland Medical Center, Baltimore, Maryland., Orens JB; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Stanford University School of Medicine, Palo Alto, California., Nathan SD; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Inova Fairfax Hospital, Fairfax, Virginia., Agbor-Enoh S; Genomic Research Alliance for Transplantation (GRAfT), 10 Center Drive, 7S261, Bethesda, Maryland; Division of Intramural Research, National Heart, Lung and Blood Institute, 10 Center Drive, 7S261, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, The Johns Hopkins School of Medicine, 1830 East Monument Street, Baltimore, Maryland. Electronic address: sean.agbor-enoh@nih.gov.
Jazyk:	angličtina
Zdroj:	The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2021 Aug; Vol. 40 (8), pp. 822-830. Date of Electronic Publication: 2021 Apr 24.
DOI:	10.1016/j.healun.2021.04.009
Abstrakt:	Background: Acute rejection, which includes antibody-mediated rejection and acute cellular rejection, is a risk factor for lung allograft loss. Lung transplant patients often undergo surveillance transbronchial biopsies to detect and treat acute rejection before irreversible chronic rejection develops. Limitations of this approach include its invasiveness and high interobserver variability. We tested the performance of percent donor-derived cell-free DNA (%ddcfDNA), a non-invasive blood test, to detect acute rejection. Methods: This multicenter cohort study monitored 148 lung transplant subjects over a median of 19.6 months. We collected serial plasma samples contemporaneously with TBBx to measure %ddcfDNA. Clinical data was collected to adjudicate for acute rejection. The primary analysis consisted of computing the area-under-the-receiver-operating-characteristic-curve of %ddcfDNA to detect acute rejection. Secondary analysis determined %ddcfDNA rule-out thresholds for acute rejection. Results: ddcfDNA levels were high after transplant surgery and decayed logarithmically. With acute rejection, ddcfDNA levels rose six-fold higher than controls. ddcfDNA levels also correlated with severity of lung function decline and histological grading of rejection. %ddcfDNA area-under-the-receiver-operating-characteristic-curve for acute rejection, AMR, and ACR were 0.89, 0.93, and 0.83, respectively. ddcfDNA levels of <0.5% and <1.0% showed a negative predictive value of 96% and 90% for acute rejection, respectively. Histopathology detected one-third of episodes with ddcfDNA levels ≥1.0%, even though >90% of these events were coincident to clinical complications missed by histopathology. Conclusions: This study demonstrates that %ddcfDNA reliably detects acute rejection and other clinical complications potentially missed by histopathology, lending support to its use as a non-invasive marker of allograft injury. (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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