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- Title
Cell-Free DNA Maps Tissue Injury and Correlates with Disease Severity in Lung Transplant Candidates.
- Authors
Balasubramanian, Shanti; Richert, Mary E.; Kong, Hyesik; Fu, Sheng; Jang, Moon Kyoo; Andargie, Temesgen E.; Keller, Michael B.; Alnababteh, Muhtadi; Park, Woojin; Apalara, Zainab; Sun, Jian; Redekar, Neelam; Orens, Jonathan; Aryal, Shambhu; Bush, Errol L.; Cantu, Edward; Diamond, Joshua; Shah, Pali; Yu, Kai; Nathan, Steven D.
- Abstract
Rationale: Plasma cell-free DNA levels correlate with disease severity in many conditions. Pretransplant cell-free DNA may risk stratify lung transplant candidates for post-transplant complications. Objectives: To evaluate if pretransplant cell-free DNA levels and tissue sources identify patients at high risk of primary graft dysfunction and other pre- and post-transplant outcomes. Methods: This multicenter, prospective cohort study recruited 186 lung transplant candidates. Pretransplant plasma samples were collected to measure cell-free DNA. Bisulfite sequencing was performed to identify the tissue sources of cell-free DNA. Multivariable regression models determined the association between cell-free DNA levels and the primary outcome of primary graft dysfunction and other transplant outcomes, including Lung Allocation Score, chronic lung allograft dysfunction, and death. Measurements and Main Results: Transplant candidates had twofold greater cell-free DNA levels than healthy control patients (median [interquartile range], 23.7 ng/ml [15.1–35.6] vs. 12.9 ng/ml [9.9–18.4]; P < 0.0001), primarily originating from inflammatory innate immune cells. Cell-free DNA levels and tissue sources differed by native lung disease category and correlated with the Lung Allocation Score (P < 0.001). High pretransplant cell-free DNA increased the risk of primary graft dysfunction (odds ratio, 1.60; 95% confidence interval [CI], 1.09–2.46; P = 0.0220), and death (hazard ratio, 1.43; 95% CI, 1.07–1.92; P = 0.0171) but not chronic lung allograft dysfunction (hazard ratio, 1.37; 95% CI, 0.97–1.94; P = 0.0767). Conclusions: Lung transplant candidates demonstrate a heightened degree of tissue injury with elevated cell-free DNA, primarily originating from innate immune cells. Pretransplant plasma cell-free DNA levels predict post-transplant complications.
- Subjects
CELL-free DNA; LUNG transplantation; SOFT tissue injuries; LUNG diseases; TREATMENT effectiveness; ALLOIMMUNITY; DNA adducts; BK virus
- Publication
American Journal of Respiratory & Critical Care Medicine, 2024, Vol 209, Issue 6, p727
- ISSN
1073-449X
- Publication type
Article
- DOI
10.1164/rccm.202306-1064OC