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dc.contributor.authorAgbor-Enoh, S.
dc.contributor.authorWang, Y.
dc.contributor.authorTunc, I.
dc.date.accessioned2019-03-29T14:47:39Z
dc.date.available2019-03-29T14:47:39Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85060510387&doi=10.1016%2fj.ebiom.2018.12.029&partnerID=40&md5=ade58930f69b7b6f7e2130d51198fb03
dc.identifier.urihttp://hdl.handle.net/10713/8725
dc.description.abstractBackground: Allograft failure is common in lung-transplant recipients and leads to poor outcomes including early death. No reliable clinical tools exist to identify patients at high risk for allograft failure. This study tested the use of donor-derived cell-free DNA (%ddcfDNA) as a sensitive marker of early graft injury to predict impending allograft failure. Methods: This multicenter, prospective cohort study enrolled 106 subjects who underwent lung transplantation and monitored them after transplantation for the development of allograft failure (defined as severe chronic lung allograft dysfunction [CLAD], retransplantation, and/or death from respiratory failure). Plasma samples were collected serially in the first three months following transplantation and assayed for %ddcfDNA by shotgun sequencing. We computed the average levels of ddcfDNA over three months for each patient (avddDNA) and determined its relationship to allograft failure using Cox-regression analysis. Findings: avddDNA was highly variable among subjects: median values were 3.6%, 1.6% and 0.7% for the upper, middle, and low tertiles, respectively (range 0.1%-9.9%). Compared to subjects in the low and middle tertiles, those with avddDNA in the upper tertile had a 6.6-fold higher risk of developing allograft failure (95% confidence interval 1.6-19.9, p = 0.007), lower peak FEV1 values, and more frequent %ddcfDNA elevations that were not clinically detectable. Interpretation: Lung transplant patients with early unresolving allograft injury measured via %ddcfDNA are at risk of subsequent allograft injury, which is often clinically silent, and progresses to allograft failure. Fund: National Institutes of Health. © 2019en_US
dc.description.sponsorshipThe Genome Transplant Dynamics Study ( NCT01985412 ) is funded by the National Institutes of Health , Grant RC4AI092673 . The Genomic Research Alliance for Transplantation Study ( NCT02423070 ) is funded by the Division of Intramural Research of the National Heart, Lung, and Blood Institute . Funders had no role in study design, data collection, data analysis, interpretation, writing of the report.en_US
dc.description.urihttps://dx.doi.org/10.1016/j.ebiom.2018.12.029en_US
dc.language.isoen_USen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofEBioMedicine
dc.subjectallograft failureen_US
dc.subjectdonor-derived cell-free DNAen_US
dc.subject.meshAllograftsen_US
dc.subject.meshBiomarkersen_US
dc.subject.meshLung Transplantation--mortalityen_US
dc.titleDonor-derived cell-free DNA predicts allograft failure and mortality after lung transplantationen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.ebiom.2018.12.029
dc.identifier.pmid30692045


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