Utility of Serial Donor-derived Cell-free DNA Measurements for Detecting Allograft Rejection in a Kidney Transplant Recipient After PD-1 Checkpoint Inhibitor Administration.
Utility of Serial Donor-derived Cell-free DNA Measurements for Detecting Allograft Rejection in a Kidney Transplant Recipient After PD-1 Checkpoint Inhibitor Administration.
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连续供体来源的无细胞DNA测量在检测PD-1检查点抑制剂给药后肾移植受者的同种异体移植排斥反应中的实用性。
DOI：
10.1097/txd.0000000000001113
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发表时间：
2021-03
影响因子：
2.3
通讯作者：
Lipson EJ
中科院分区：
文献类型：
--
作者：
Lakhani L;Alasfar S;Bhalla A;Aala A;Rosenberg A;Ostrander D;Schollenberger MD;Brennan DC;Lipson EJ
供体来源的细胞游离DNA（dd-cfDNA）是源自经历损伤的同种异体移植细胞的排斥反应的有用生物标志物。肾移植受者血浆水平<1%对主动性同种异体移植排斥反应具有较高的阴性预测值。这种生物标志物在接受免疫检查点抑制剂治疗的肾移植受者中的效用尚不清楚。我们描述了一个病例，其中连续dd-cfDNA监测促进了免疫检查点抑制剂治疗的使用，已知免疫检查点抑制剂治疗与转移性癌症肾移植受者的高排斥率相关。一名72岁的男性，患有常染色体显性多囊肾病继发的终末期肾病，于2010年12月接受了活体无关肾移植。他的免疫抑制方案包括他克莫司、霉酚酸酯和泼尼松。2017年7月，患者出现转移性皮肤鳞状细胞癌。在他的疾病通过放射治疗和西妥昔单抗进展后，他接受了pembrolizumab（抗程序性细胞死亡蛋白1）。他的dd-cfDNA水平在基线时检测不到，然后在治疗期间增加，但仍<1%。尽管治疗期间血清肌酐水平波动，但这种趋势允许继续使用pembrolizumab并成功治疗他的转移性癌症，而没有临床上明显的同种异体移植物排斥反应。停用派姆单抗后，dd-cfDNA水平降至检测水平以下。皮肤鳞状细胞癌的遗传分析显示了与dd-cfDNA不同的遗传特征，表明肿瘤裂解不影响dd-cfDNA的增加。连续dd-cfDNA测量可以提供用于检测同种异体移植物损伤的有用的非侵入性生物标志物，其可以促进在患有癌症的器官移植受者中使用免疫调节疗法。
Donor-derived cell-free DNA (dd-cfDNA) is a useful biomarker of rejection that originates from allograft cells undergoing injury. Plasma levels <1% in kidney transplant recipients have a high negative predictive value for active allograft rejection. The utility of this biomarker in kidney transplant recipients receiving immune checkpoint inhibitor therapy is unknown. We describe a case in which serial dd-cfDNA monitoring facilitated the use of immune checkpoint inhibitor therapy, which is known to be associated with high rates of rejection, in a kidney transplant recipient with metastatic cancer. A 72-y-old man with end-stage kidney disease secondary to autosomal dominant polycystic kidney disease underwent living unrelated kidney transplant in December 2010. His immunosuppression regimen included tacrolimus, mycophenolate, and prednisone. In July 2017, he presented with metastatic cutaneous squamous cell carcinoma. After his disease progressed through radiation therapy and cetuximab, he received pembrolizumab (antiprogrammed cell death protein 1). His dd-cfDNA level was undetectable at baseline, then increased during treatment but remained <1%. This trend, despite fluctuations in serum creatinine levels during therapy, allowed for continuation of pembrolizumab and successful treatment of his metastatic cancer without clinically evident allograft rejection. After discontinuation of pembrolizumab, dd-cfDNA levels fell below the level of detection. Genetic analysis of the cutaneous squamous cell carcinoma demonstrated a genetic profile distinct from the dd-cfDNA, indicating that tumor lysis did not impact increases in dd-cfDNA. Serial dd-cfDNA measurements may provide a useful, noninvasive biomarker for detecting allograft injury that may facilitate the use of immunomodulatory therapies in organ transplant recipients with cancer.