Sayah David, Weigt S Samuel, Ramsey Allison, Ardehali Abbas, Golden Jeff, Ross David J
Division of Pulmonary, Critical Care Medicine, Allergy & Immunology, David Geffen-UCLA School of Medicine, Los Angeles, CA.
Division Cardiothoracic Surgery, David Geffen-UCLA School of Medicine, Los Angeles, CA.
Transplant Direct. 2020 Sep 24;6(10):e608. doi: 10.1097/TXD.0000000000001063. eCollection 2020 Oct.
Telehealth platforms with remote phlebotomy and biomarker implementation represent a novel paradigm for surveillance after lung transplantation (LT). In a pilot study, we investigated donor-derived cell-free DNA (dd-cfDNA) in plasma using a clinical-grade "next-generation sequencing" assay.
dd-cfDNA levels determined in biorepository venous plasma samples obtained during the lung allograft rejection gene expression observation study, implementing a clinical-grade next-generation sequencing assay. Sixty-nine unique LT patients encompassing 9 LT centers, with associated clinical-histopathologic diagnoses, were examined-allograft infection (n = 26), normal histopathology without infection (n = 30), and acute cellular rejection (ACR; n = 13).
dd-cfDNA in ACR patients were significantly elevated (1.52%; interquartile range [IQR], 0.520-2.2550) compared with the normal stable patients (0.485%; IQR, 0.220-0.790) ( = 0.026). During allograft infection, dd-cfDNA values were not different (0.595; IQR, 0.270-1.170) from normal ( = 0.282) and ACR ( = 0.100). AUC-receiver operator characteristics curve analysis for allograft ACR was 0.717 (95% confidence interval, 0.547-0.887; = 0.025). At a 0.87% threshold dd-cfDNA-sensitivity = 73.1%, specificity = 52.9%, positive predictive value = 34.1%, and negative predictive value = 85.5%.
dd-cfDNA assessment holds promise as a noninvasive biomarker of "allograft injury" with acute rejection following LT while prospective, multicenter studies should further refine utility across the spectrum of allograft rejection and infection.
具备远程静脉穿刺和生物标志物检测功能的远程医疗平台代表了肺移植（LT）术后监测的一种新范例。在一项试点研究中，我们使用临床级“下一代测序”检测方法对血浆中供体来源的游离DNA（dd-cfDNA）进行了研究。
在肺移植排斥反应基因表达观察研究期间，从生物样本库的静脉血浆样本中测定dd-cfDNA水平，采用临床级下一代测序检测方法。对来自9个LT中心的69例独特的LT患者进行了检查，这些患者有相关的临床组织病理学诊断，包括同种异体移植感染（n = 26）、无感染的正常组织病理学（n = 30）和急性细胞排斥反应（ACR；n = 13）。
与正常稳定患者（0.485%；四分位间距[IQR]，0.220 - 0.790）相比，ACR患者的dd-cfDNA显著升高（1.52%；IQR，0.520 - 2.2550）（P = 0.026）。在同种异体移植感染期间，dd-cfDNA值与正常患者（P = 0.282）和ACR患者（P = 0.100）相比无差异（0.595；IQR，0.270 - 1.170）。同种异体移植ACR的AUC-受试者操作特征曲线分析为0.717（95%置信区间，0.547 - 0.887；P = 0.025）。在dd-cfDNA阈值为0.87%时，敏感性 = 73.1%，特异性 = 52.9%，阳性预测值 = 34.1%，阴性预测值 = 85.5%。
dd-cfDNA评估有望成为LT术后急性排斥反应时“同种异体移植损伤”的一种非侵入性生物标志物，而前瞻性多中心研究应进一步完善其在同种异体移植排斥反应和感染范围内的应用。
