Introduction

Antibody-mediated rejection (ABMR) is a major cause of kidney transplant failure which requires donor-specific antibodies (DSA) for a definitive diagnosis. Donor-derived cell-free DNA (ddcfDNA) is an emerging biomarker used to assess kidney allograft injury. However, current data is limited to predict the accuracy of ddcfDNA in ABMR diagnosis. This study was conducted to compare the performance of DSA with plasma ddcfDNA for the diagnosis of ABMR.

Methods

In this retrospective single-center observational study, we enrolled 50 kidney transplant recipients who were diagnosed with the suspicion of rejection between June 2018 and May 2019 at the Jinling Hospital. Plasma ddcfDNA was measured by using a novel target region capture sequencing methodology. A total of 37 patients who were tested with DSA and biopsy were divided into four subgroups (ABMR+/DSA+, ABMR+/DSA-, ABMR-/DSA+, ABMR-/DSA-) for the distribution of ddcfDNA (%) by ABMR and DSA.

Results

The median level of ddcfDNA in biopsy showed that the ABMR group (1.66%, IQR 1.34–3.76%) was significantly higher than the median level (0.63%, IQR 0.43–0.74%) in non-ABMR (p < 0.001). With a ddcfDNA cutoff of 0.96%, the AUC was 0.90 (95%CI, 0.86–0.95), which was associated with a sensitivity of 90.5% (95%CI, 69.6–98.8%) and specificity of 96.6% (95%CI, 82.2–100%), a PPV of 95% (95%CI, 73.4–99.2%) and NPV of 93.3% (95%CI, 78.9–98.1%) were also observed. Among the four subgroups, ddcfDNA had no significant difference in both DSA+ group and DSA-group (p > 0.05). In the diagnosis of ABMR, the specificity, sensitivity, PPV and NPV of DSA were 50%, 74.1%, 41.7%, 80%, respectively.

Conclusions

ddcfDNA levels in the blood could highly distinguish (biopsy-supported) ABMR occurrence, irrespective of whether this method is accompanied by DSA or not.

中文翻译：

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供体来源的游离 DNA：具有抗体介导排斥反应的肾移植患者的独立生物标志物

介绍

抗体介导的排斥反应 (ABMR) 是肾移植失败的主要原因，需要供体特异性抗体 (DSA) 才能明确诊断。供体来源的无细胞 DNA (ddcfDNA) 是一种新兴的用于评估同种异体移植肾损伤的生物标志物。然而，目前的数据仅限于预测 ddcfDNA 在 ABMR 诊断中的准确性。本研究旨在比较 DSA 与血浆 ddcfDNA 在诊断 ABMR 方面的性能。

方法

在这项回顾性单中心观察性研究中，我们在 2018 年 6 月至 2019 年 5 月期间在金陵医院招募了 50 名被诊断为疑似排斥反应的肾移植受者。血浆 ddcfDNA 通过使用一种新的目标区域捕获测序方法进行测量。共有 37 名接受 DSA 和活检检测的患者分为 4 个亚组（ABMR+/DSA​​+、ABMR+/DSA​​-、ABMR-/DSA+、ABMR-/DSA-），根据 ABMR 和 DSA 的 ddcfDNA (%) 分布.

结果

活检中 ddcfDNA 的中位水平显示 ABMR 组（1.66%，IQR 1.34–3.76%）显着高于非 ABMR 组的中位水平（0.63%，IQR 0.43–0.74%）（p  < 0.001）。ddcfDNA 截止值为 0.96%，AUC 为 0.90 (95%CI, 0.86–0.95)，与 90.5% (95%CI, 69.6–98.8%) 的敏感性和 96.6% (95%CI) 的特异性相关, 82.2–100%), PPV 为 95% (95%CI, 73.4–99.2%) 和 NPV 为 93.3% (95%CI, 78.9–98.1%)。4个亚组中，ddcfDNA在DSA+组和DSA-组均无显着差异（p  >0.05）。在诊断ABMR中，DSA的特异性、敏感性、PPV和NPV分别为50%、74.1%、41.7%、80%。

结论

血液中的 ddcfDNA 水平可以高度区分（活检支持的）ABMR 的发生，无论这种方法是否伴有 DSA。