Background: Donor-derived cell free DNA (ddcf DNA) has been reported as\na universal noninvasive biomarker for rejection monitoring in heart, kidney,\nliver, and lung transplantation. Current approaches based on next-generation\nsequencing for quantification of ddcf DNA, although promising, may be restricted\nby the requirement for donor material, as donor samples may not be\navailable. Methods: We proposed a novel next-generation sequencing approach\nwithout donor-derived material and compared the non-donor-derived\napproach and the donor-derived approach using simulation testing and 69\nclinical specimens. We also evaluated the performance for acute rejection and\ninfection monitoring in lung transplantation. Results: The non-donor-derived\napproach reached similar efficacy as the donor-derived approach with a significant\nlinear correlation of R2 = 0.98. Subsequent validation in clinical specimens\ndemonstrated significant difference between the acute rejection group (4.83% ± 2.11%, mean ± SD) and the non-rejection group (1.61% ±\n0.63%, mean ± SD) (P < 0.0001, Welchâ??s t test). With the cut-off value of\n2.999, our approach had 90.48% sensitivity (95% CI, 69.62% - 98.83%), 100%\nspecificity (95% CI, 91.59% - 100%), and AUC 0.9266 (95% CI, 0.8277 -\n1.026). The test also had the ability to simultaneously detect infectious agents,\nespecially cytomegalovirus, as compared with the clinical test. Conclusion:\nThe proposed approach without donor-derived material could potentially be\nused to monitor acute rejection and infection in lung transplantation and\nmay be applied to other types of solid organ transplantation.
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