Clinical Validation of a Plasma Donor-derived Cell-free DNA Assay to Detect Allograft Rejection and Injury in Lung Transplant.
Journal
Transplantation direct
ISSN: 2373-8731
Titre abrégé: Transplant Direct
Pays: United States
ID NLM: 101651609
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
24
12
2021
revised:
04
02
2022
accepted:
26
02
2022
entrez:
4
4
2022
pubmed:
5
4
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Lung transplant patients are vulnerable to various forms of allograft injury, whether from acute rejection (AR) (encompassing acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), chronic lung allograft dysfunction (CLAD), or infection (INFXN). Previous research indicates that donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker for the detection of AR and allograft injury. Our aim was to validate a clinical plasma dd-cfDNA assay for detection of AR and other allograft injury and to confirm and expand on dd-cfDNA and allograft injury associations observed in previous studies. We measured dd-cfDNA fraction using a novel single-nucleotide polymorphism-based assay in prospectively collected plasma samples paired with clinical-pathologic diagnoses. dd-cfDNA fraction was compared across clinical-pathologic cohorts: stable, ACR, AMR, isolated lymphocytic bronchiolitis, CLAD/neutrophilic-responsive allograft dysfunction (NRAD), and INFXN. Performance characteristics were calculated for AR and combined allograft injury (AR + CLAD/NRAD + INFXN) versus the stable cohort. The study included 195 samples from 103 patients. Median dd-cfDNA fraction was significantly higher for ACR (1.43%, interquartile range [IQR]: 0.67%-2.32%, These results indicate that our dd-cfDNA assay detects AR and other allograft injury. dd-cfDNA monitoring, accompanied by standard clinical assessments, represents a valuable precision tool to support lung transplant health and is appropriate for further assessment in a prospective randomized-controlled study.
Sections du résumé
Background
UNASSIGNED
Lung transplant patients are vulnerable to various forms of allograft injury, whether from acute rejection (AR) (encompassing acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), chronic lung allograft dysfunction (CLAD), or infection (INFXN). Previous research indicates that donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker for the detection of AR and allograft injury. Our aim was to validate a clinical plasma dd-cfDNA assay for detection of AR and other allograft injury and to confirm and expand on dd-cfDNA and allograft injury associations observed in previous studies.
Methods
UNASSIGNED
We measured dd-cfDNA fraction using a novel single-nucleotide polymorphism-based assay in prospectively collected plasma samples paired with clinical-pathologic diagnoses. dd-cfDNA fraction was compared across clinical-pathologic cohorts: stable, ACR, AMR, isolated lymphocytic bronchiolitis, CLAD/neutrophilic-responsive allograft dysfunction (NRAD), and INFXN. Performance characteristics were calculated for AR and combined allograft injury (AR + CLAD/NRAD + INFXN) versus the stable cohort.
Results
UNASSIGNED
The study included 195 samples from 103 patients. Median dd-cfDNA fraction was significantly higher for ACR (1.43%, interquartile range [IQR]: 0.67%-2.32%,
Conclusions
UNASSIGNED
These results indicate that our dd-cfDNA assay detects AR and other allograft injury. dd-cfDNA monitoring, accompanied by standard clinical assessments, represents a valuable precision tool to support lung transplant health and is appropriate for further assessment in a prospective randomized-controlled study.
Identifiants
pubmed: 35372675
doi: 10.1097/TXD.0000000000001317
pmc: PMC8963832
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e1317Informations de copyright
Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
A.B., B.G.Z., D.J.R., E.A., G.F., J.S., N.L., M.O., R.S., Z.P.D., Y.-A.C., and P.R.B. are full-time employees at Natera Inc. with stocks or options to own stocks in the company. B.C.K. serves as a consultant to and on the speaker bureau for CareDx, Inc. and has received research funding from CareDx, Natera, and Zambon. J.P.R. has received research funding from Natera. The other authors declare no conflicts of interest.
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