Application of plasma donor-derived cell free DNA for lung allograft rejection diagnosis in lung transplant recipients

Abstract

Abstract Background Donor-derived cell-free DNA (dd-cfDNA) has been applied to monitor acute rejection (AR) in kidney and heart transplantation. This study was aimed to investigate the application of dd-cfDNA levels in the diagnosis of AR and chronic lung allograft dysfunction (CLAD) among the lung transplantation recipients (LTRs). Methods One hundred and seventy LTRs were enrolled at the First Affiliated Hospital of Guangzhou Medical University between 1 June 2015 and 30 March 2021. Patients were divided into 4 groups: stable group, AR group, infection group and CLAD group. The level of dd-cfDNA was analyzed using target region sequencing and the performance characteristics of dd-cfDNA for diagnosis of AR and CLAD were determined, respectively. Results Kruskal–Wallis test showed that there were some significant differences in the level of dd-cfDNA (%) among the 4 groups, with p < 0.001. Among them, the level of dd-cfDNA (%) was highest (median 2.17, IQR [1.40–3.82]) in AR group, and higher in CLAD group (median 1.07, IQR [0.98–1.31]), but lower in infection group (median 0.71, IQR [0.57–1.07]) and lowest in stable group (median 0.71, IQR [0.61–0.84]). AUC-ROC curve analysis showed that the threshold of dd-cfDNA for AR was 1.17%, with sensitivity being 89.19% and specificity being 86.47%, and the optimal threshold of 0.89% was determined of CLAD, with sensitivity being 95.00% and specificity of 76.99%. Conclusions Plasma dd-cfDNA could be a useful tool for the assessment of lung allograft rejection, including AR and CLAD, and holds promise as a noninvasive biomarker for “allograft injury” in both acute and chronic rejection following lung transplantation.