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.
Clin Transplant. 2024 Oct;38(10):e15479. doi: 10.1111/ctr.15479.
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.
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.
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.
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.
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。
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。
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。
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。
