Beeckmans H, Pagliazzi A, Kerckhof P, Hofkens R, Debackere F, Zajacova A, Bos S, Vanaudenaerde B M, de Loor H, Naesens M, Vos R
Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of CHROMETA, KU Leuven, Leuven, Belgium.
Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Front Transplant. 2024 Dec 23;3:1513101. doi: 10.3389/frtra.2024.1513101. eCollection 2024.
Long-term survival after lung transplantation is limited due to chronic lung allograft dysfunction (CLAD), which encompasses two main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Donor-derived cell-free DNA (dd-cfDNA) is a biomarker for (sub)clinical allograft injury and could be a tool for monitoring of lung allograft health across the (pre)clinical spectrum of CLAD. In this proof-of-concept study, we therefore assessed post-transplant plasma dd-cfDNA levels in 20 CLAD patients (11 BOS and 9 RAS) at three consecutive time points free from concurrent infection or acute rejection, during stable condition, preclinical CLAD, and established CLAD ( = 3 × 20 samples). Elevated dd-cfDNA levels were detected in 47% of stable samples, in 66% of preclinical CLAD samples, and in 71% of CLAD samples, indicating ongoing allograft injury. However, dd-cfDNA levels exhibited high intra- and interpatient variability and did not significantly differ between BOS and RAS ( = 0.25), although the range of dd-cfDNA was higher in RAS. Dd-cfDNA detects ongoing allograft injury in patients with CLAD, which warrants further investigation to improve early detection of CLAD.
由于慢性肺移植功能障碍（CLAD），肺移植后的长期生存受到限制，CLAD包括两种主要表型：闭塞性细支气管炎综合征（BOS）和限制性移植综合征（RAS）。供体来源的游离DNA（dd-cfDNA）是（亚）临床移植损伤的生物标志物，可能是一种在CLAD的（临床前）全谱范围内监测肺移植健康状况的工具。因此，在这项概念验证研究中，我们在三个连续时间点评估了20例CLAD患者（11例BOS和9例RAS）移植后的血浆dd-cfDNA水平，这些时间点均无并发感染或急性排斥反应，处于稳定状态、临床前CLAD和确诊CLAD阶段（=3×20个样本）。在47%的稳定样本、66%的临床前CLAD样本和71%的CLAD样本中检测到dd-cfDNA水平升高，表明移植肺持续受到损伤。然而，dd-cfDNA水平在患者内和患者间表现出高度变异性，且在BOS和RAS之间无显著差异（=0.25），尽管RAS中dd-cfDNA的范围更高。Dd-cfDNA可检测CLAD患者移植肺的持续损伤，这值得进一步研究以改善CLAD的早期检测。
