多器官移植的心脏移植受者供体来源无细胞 DNA 的临床应用。
Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants.
机构信息
Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, USA.
Department of Cardiothoracic Surgery, Columbia University Irving Medical Center, New York, USA.
出版信息
Clin Transplant. 2024 Oct;38(10):e15479. doi: 10.1111/ctr.15479.
BACKGROUND
Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients.
METHODS
A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected. Patients who had simultaneous MOT were identified and included in this study. Levels of dd-cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade ≥ 2R. and antibody-mediated rejection (AMR) was defined as pAMR grade > 0. The within-patient variability score of the dd-cfDNA was calculated by the variance/average.
RESULTS
The study included 25 multiorgan transplant recipients: 13 heart-kidney (H-K), 8 heart-liver (H-Li), and 4 heart-lung (H-Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd-cfDNA measurement was 4.5 months (IQR 2, 10.5). The median dd-cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H-K, 1.15% (IQR 0.77%, 2.33%) for H-Li, and 0.69% (IQR 0.62%, 1.07%) for H-Lu patients (p < 0.001). Prevalence of positive dd-cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H-K, H-Li, and H-Lu groups, respectively. The within-patient variability score was highest in the H-Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H-K group (median of 0.09 [IQR 0.06, 0.12]); p = 0.002. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR-mediated lung rejection. One person in the H-K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy-confirmed rejection.
CONCLUSION
Dd-cfDNA is chronically elevated in most MOT recipients. There is a high degree of within-patient variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in monitoring MOT recipients.
背景
供体来源的无细胞游离 DNA（dd-cfDNA）已成为监测心脏移植（HT）患者同种异体移植排斥的可靠、非侵入性方法，但在多器官移植（MOT）中的应用尚不清楚。我们描述了在同时接受 MOT 的患者中使用 dd-cfDNA 的经验。
方法
对 2018 年至 2022 年间至少进行了一次 dd-cfDNA 测量的所有 HT 受者进行了单中心回顾性研究。如果有条件，对同时接受 MOT 的患者进行识别并纳入本研究。dd-cfDNA 水平与血液检测后 1 个月内进行的心肌活检（EMB）进行配对。急性细胞排斥（ACR）定义为国际心肺移植协会（ISHLT）分级≥2R。抗体介导的排斥（AMR）定义为 pAMR 分级>0。dd-cfDNA 的患者内变异性评分通过方差/平均值计算。
结果
该研究纳入了 25 名多器官移植受者：13 名心脏-肾脏（H-K）、8 名心脏-肝脏（H-Li）和 4 名心脏-肺（H-Lu）。中位年龄为 55 岁，44%为女性；从 HT 到第一次 dd-cfDNA 测量的中位时间为 4.5 个月（IQR 2，10.5）。H-K、H-Li 和 H-Lu 患者的中位 dd-cfDNA 水平分别为 0.18%（IQR 0.15%，0.27%）、1.15%（IQR 0.77%，2.33%）和 0.69%（IQR 0.62%，1.07%）（p<0.001）。dd-cfDNA 检测呈阳性的患者比例（阈值为 0.20%）分别为 H-K 组 42.2%、H-Li 组 97.3%和 H-Lu 组 92.3%。H-Li 组的患者内变异性评分最高（中位数为 0.45 [IQR 0.29，0.94]），H-K 组最低（中位数为 0.09 [IQR 0.06，0.12]）；p=0.002。未发现心脏 ACR 或 AMR 的证据。3 名患者发生肾移植排斥反应和/或 AMR，2 名患者发生肝移植排斥反应，1 名患者发生 AMR 介导的肺排斥反应。H-K 组 1 名患者发生心脏移植排斥反应，但与活检证实的排斥无关。
结论
dd-cfDNA 在大多数 MOT 受者中持续升高。水平的患者内变异性很大（特别是对于 H-Li 和 H-Lu 受者），这可能限制了该检测在监测 MOT 受者中的应用。
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