Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Respiratory Medicine, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
Immun Inflamm Dis. 2022 May;10(5):e620. doi: 10.1002/iid3.620.
Lung transplantation (LTx) is a lifesaving procedure burdened with limited long-term survival. The most common cause of death after LTx is chronic lung allograft dysfunction (CLAD). Today, useful biomarkers for the detection of CLAD are lacking. Circulating cell-free DNA (cfDNA) is released during cellular decay and can be detected using polymerase chain reaction (PCR). Thus, donor-derived cfDNA in recipient serum indicates cellular decay in the transplanted organ. In the current study, we explore the possibility of using a novel PCR method to detect cfDNA as a biomarker for clinical events, especially CLAD.
Four patients were retrospectively tested for levels of both donor and recipient-derived cfDNA using digital droplet PCR after targeted preamplification. The results were correlated to recorded clinical events.
All available samples rendered results. Both patients that later developed CLAD showed a persistently elevated ratio between donor-and recipient-derived cfDNA. Also, the mean level of cfDNA was higher in the two patients who later developed CLAD than in patients who did not (p = .0015).
This proof-of-concept study suggests that cfDNA quantified with PCR may be used as a biomarker of significant clinical events such as CLAD.
肺移植（LTx）是一种挽救生命的手术，但长期存活率有限。LTx 后最常见的死亡原因是慢性肺移植物功能障碍（CLAD）。目前，缺乏用于检测 CLAD 的有用生物标志物。循环无细胞 DNA（cfDNA）在细胞衰亡时释放，可以通过聚合酶链反应（PCR）检测到。因此，受体血清中的供体源性 cfDNA 表明移植器官中的细胞衰亡。在当前的研究中，我们探索了使用新型 PCR 方法检测 cfDNA 作为临床事件（尤其是 CLAD）生物标志物的可能性。
对 4 名患者使用靶向预扩增后的数字液滴 PCR 检测供体和受体来源 cfDNA 的水平，并将结果与记录的临床事件相关联。
所有可用样本均得出结果。随后发展为 CLAD 的两名患者均显示供体和受体来源 cfDNA 之间的比值持续升高。此外，随后发展为 CLAD 的两名患者的 cfDNA 平均水平高于未发展为 CLAD 的患者（p =.0015）。
这项概念验证研究表明，用 PCR 定量的 cfDNA 可能可作为 CLAD 等重要临床事件的生物标志物。
