A Novel Next-Generation Sequencing Approach without Donor-Derived Material for Acute Rejection and Infection Monitoring in Solid Organ Transplantation

• 作者: Bing Wei Chunrong Ju Chunting Zheng Danxia Huang Di Shao Dong Xiao Jian Wang Jianxing He Jibin Zhang Karsten Kristiansen Liping Liu Liuhong Zeng Mingzhi Ye Qing Yang Qiuhua Deng Wenhua Liang Xin Xu Yongping Lin
• 来源期刊: 癌症治疗(英文)
• 学科: 医学
• 关键词: CELL-FREE DNA GENOME TRANSPLANT Dynamics Acute REJECTION TRANSPLANT INFECTION
• 年，卷（期）: azzlyw_2018,（9）
• 页码范围: 623-638
• 页数: 16页
• 分类号: R73

摘要

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.