TITLE:
A Novel Next-Generation Sequencing Approach without Donor-Derived Material for Acute Rejection and Infection Monitoring in Solid Organ Transplantation
AUTHORS:
Bing Wei, Liuhong Zeng, Di Shao, Chunting Zheng, Qing Yang, Jibin Zhang, Dong Xiao, Qiuhua Deng, Yongping Lin, Danxia Huang, Liping Liu, Xin Xu, Wenhua Liang, Chunrong Ju, Jian Wang, Karsten Kristiansen, Jianxing He, Mingzhi Ye
KEYWORDS:
Cell-Free DNA, Genome Transplant Dynamics, Acute Rejection, Transplant, Infection
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.9 No.9,
September
5,
2018
ABSTRACT: Background: Donor-derived cell free DNA (ddcf
DNA) has been reported as a universal noninvasive biomarker for rejection monitoring
in heart, kidney, liver, and lung transplantation. Current approaches based on next-generation
sequencing for quantification of ddcf DNA, although promising, may be restricted
by the requirement for donor material, as donor samples may not be available. Methods:
We proposed a novel next-generation sequencing approach without donor-derived material and compared the non-donor-derived approach and the donor-derived approach using simulation testing and 69 clinical
specimens. We also evaluated the performance for acute rejection and infection monitoring in lung transplantation. Results: The non-donor-derived approach reached similar efficacy as the donor-derived
approach with a significant linear correlation of R2 = 0.98. Subsequent validation in clinical specimens
demonstrated significant difference between the acute rejection group (4.83% ± 2.11%, mean
± SD) and the non-rejection group (1.61% ± 0.63%, mean ± SD) (P ’s t test). With the cut-off
value of 2.999, our approach had 90.48% sensitivity (95% CI, 69.62% - 98.83%), 100%
specificity (95% CI, 91.59% - 100%), and AUC 0.9266 (95% CI, 0.8277 - 1.026). The
test also had the ability to simultaneously detect infectious agents, especially
cytomegalovirus, as compared with the clinical test. Conclusion: The proposed
approach without donor-derived material could potentially be used to monitor acute
rejection and infection in lung transplantation and may be applied to other types
of solid organ transplantation.