Extracellular vesicles in lung donor plasma: Potential indicators of donor organ quality

Objective: Brain death induces systemic inflammation and hemodynamic changes that can lead to lung injury, impacting the quality of donor organs for transplantation. Extracellular vesicles (EVs) are cell-derived nanoparticles that carry functional biomolecules and reflect the physiological state of their cells of origin. We hypothesized that EVs from brain-dead donors may indicate lung injury and may be used to predict primary graft dysfunction (PGD) in lung transplant recipients. Methods: We performed transcriptomic profiling of plasma EVs from 44 brain-dead lung donors and 9 healthy controls using next-generation sequencing. Differential gene expression was assessed, followed by pathway enrichment analyses. The results were validated by quantitative polymerase chain reaction using the study cohort and an independent cohort. Variable importance of projection score analysis and regression models were used to identify EV transcripts associated with PGD in recipients. Results: Transcriptomic analysis revealed that 13% of protein-coding genes were differentially expressed in lung donor EVs compared with controls, with 92% of these genes upregulated. Upregulated genes were enriched in pathways related to inflammation, coagulation, tissue remodeling, and metabolism. Seven key EV transcripts, RAD51D, ABL2, FGFR1, WDR82, PTBP3, OPRL1, and XG were identified as potential PGD indicator. These transcripts were associated with processes such as DNA damage repair, signal transduction, and inflammation, which may contribute to posttransplant lung injury. Conclusions: Donor plasma EVs carry distinct transcriptomic signatures associated with injury and inflammation. Specific EV transcripts, such as RAD51D and XG, hold promise as independent predictive biomarkers for PGD, possibly providing new tools for evaluating donor organ quality and improving lung transplant outcomes.