Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor?Associated Adverse Events
Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor?Associated Adverse Events
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DOI：
10.2215/cjn.00920121
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发表时间：
2021-09-01
影响因子：
9.8
通讯作者：
Mengel, Michael
中科院分区：
文献类型：
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作者：
Adam, Benjamin A.;Murakami, Naoka;Mengel, Michael
背景和目的免疫检查点抑制剂越来越多地用于治疗各种恶性肿瘤，但它们在肾移植患者中的应用因高同种异体移植排斥率而复杂化。免疫检查点抑制剂？相关性排斥反应是一种新的、尚不清楚的实体，表现出与免疫检查点抑制剂重叠的组织病理学特征。相关性急性间质性肾炎，对诊断和临床治疗提出了挑战。我们试图通过基于活检的基因表达分析来提高对这些实体的理解。设计、设置、参与者和测量NanoString用于测量和比较75份肾活检档案中725个免疫相关基因的表达，其中包括25个样本发现队列，包括纯T细胞？介导的排斥反应和免疫检查点抑制剂？相关急性间质性肾炎和一个独立的50个样本验证队列，包括免疫检查点抑制剂？相关性急性间质性肾炎，免疫检查点抑制剂？关联T细胞？介导的排斥反应，免疫检查点抑制剂？相关新月形GN、药物性急性间质性肾炎、BK病毒肾病和正常活检。结果免疫检查点抑制剂？急性间质性肾炎与T细胞？介导的排斥。然而，IFI27，一个IFN-?？诱导转录物被鉴定并验证为鉴别免疫检查点抑制剂的一种新的生物标志物。关联T细胞？免疫检查点抑制剂介导的排斥反应？相关性急性间质性肾炎(验证队列：P
Background and objectives Immune checkpoint inhibitors are increasingly used to treat various malignancies, but their application in patients with kidney transplants is complicated by high allograft rejection rates. Immune checkpoint inhibitor?associated rejection is a novel, poorly understood entity demonstrating overlapping histopathologic features with immune checkpoint inhibitor?associated acute interstitial nephritis, which poses a challenge for diagnosis and clinical management. We sought to improve the understanding of these entities through biopsy-based gene expression analysis.Design, setting, participants, & measurements NanoString was used to measure and compare the expression of 725 immune-related genes in 75 archival kidney biopsies, including a 25-sample discovery cohort comprising pure T cell?mediated rejection and immune checkpoint inhibitor?associated acute interstitial nephritis and an independent 50-sample validation cohort comprising immune checkpoint inhibitor?associated acute interstitial nephritis, immune checkpoint inhibitor?associated T cell?mediated rejection, immune checkpoint inhibitor?associated crescentic GN, drug-induced acute interstitial nephritis, BK virus nephropathy, and normal biopsies.Results Significant molecular overlap was observed between immune checkpoint inhibitor?associated acute interstitial nephritis and T cell?mediated rejection. Nevertheless, IFI27, an IFN-??induced transcript, was identified and validated as a novel biomarker for differentiating immune checkpoint inhibitor?associated T cell?mediated rejection from immune checkpoint inhibitor?associated acute interstitial nephritis (validation cohort: P