Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Genomic Research Alliance for Transplantation (GRAfT) and Laboratory of Applied Precision Omics, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, United States.
Transpl Int. 2024 Jun 11;37:12445. doi: 10.3389/ti.2024.12445. eCollection 2024.
While allograft rejection (AR) continues to threaten the success of cardiothoracic transplantation, lack of accurate and repeatable surveillance tools to diagnose AR is a major unmet need in the clinical management of cardiothoracic transplant recipients. Endomyocardial biopsy (EMB) and transbronchial biopsy (TBBx) have been the cornerstone of rejection monitoring since the field's incipience, but both suffer from significant limitations, including poor concordance of biopsy interpretation among pathologists. In recent years, novel molecular tools for AR monitoring have emerged and their performance characteristics have been evaluated in multiple studies. An international working group convened by ESOT has reviewed the existing literature and provides a series of recommendations to guide the use of these biomarkers in clinical practice. While acknowledging some caveats, the group recognized that Gene-expression profiling and donor-derived cell-free DNA (dd-cfDNA) may be used to rule out rejection in heart transplant recipients, but they are not recommended for cardiac allograft vasculopathy screening. Other traditional biomarkers (NT-proBNP, BNP or troponin) do not have sufficient evidence to support their use to diagnose AR. Regarding lung transplant, dd-cfDNA could be used to rule out clinical rejection and infection, but its use to monitor treatment response is not recommended.
虽然同种异体移植排斥(AR)仍然威胁着心胸器官移植的成功,但缺乏准确且可重复的监测工具来诊断 AR,这是心胸器官移植受者临床管理中的一个主要未满足的需求。自该领域开始以来,心肌内膜活检(EMB)和经支气管活检(TBBx)一直是排斥监测的基石,但两者都存在明显的局限性,包括病理学家之间的活检解释一致性差。近年来,出现了用于 AR 监测的新型分子工具,并且已经在多项研究中评估了它们的性能特征。ESOT 召集的一个国际工作组审查了现有文献,并提出了一系列建议,以指导这些生物标志物在临床实践中的使用。尽管存在一些注意事项,但该工作组认识到,基因表达谱和供体游离 DNA(dd-cfDNA)可用于排除心脏移植受者的排斥反应,但不建议用于筛查心脏同种异体血管病。其他传统的生物标志物(NT-proBNP、BNP 或肌钙蛋白)没有足够的证据支持其用于诊断 AR。关于肺移植,dd-cfDNA 可用于排除临床排斥和感染,但不建议用于监测治疗反应。