Donor-derived cell-free DNA predicts allograft failure and mortality after lung transplantation
| Autor: | Aldo Iacono, K. Bhatti, Steven D. Nathan, Helen Luikart, Yan Wang, Ilker Tunc, Kiran K. Khush, A. Marishta, Pali D. Shah, David Grimm, C. Marboe, I. Timofte, Stephen R. Quake, Iwijn De Vlaminck, Jun Zhu, Yanqin Yang, Anne Brown, Gerald J. Berry, Sean Agbor-Enoh, S. Gorham, Jonathan B. Orens, Moon Kyoo Jang, Natalie Goodwin, Hannah A. Valantine, Andrew M. Davis, U. Fideli, K. Patel, Jennifer Wylie |
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| Rok vydání: | 2019 |
| Předmět: |
Graft Rejection
Male 0301 basic medicine medicine.medical_specialty Time Factors Research paper medicine.medical_treatment Comorbidity Kaplan-Meier Estimate Gastroenterology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Risk Factors Internal medicine medicine Humans Transplantation Homologous Lung transplantation Prospective Studies Prospective cohort study Aged Proportional Hazards Models Lung business.industry Proportional hazards model Sequence Analysis DNA General Medicine Middle Aged Allografts Prognosis medicine.disease Tissue Donors Confidence interval 3. Good health Transplantation surgical procedures operative 030104 developmental biology medicine.anatomical_structure Respiratory failure 030220 oncology & carcinogenesis Female business Cell-Free Nucleic Acids Biomarkers Lung Transplantation |
| Zdroj: | EBioMedicine |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2018.12.029 |
| Popis: | Background 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. |
| Databáze: | OpenAIRE |
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