Zubair Haseeb, Azim Shafquat, Maluf Daniel G, Mas Valeria R, Martins Paulo N
Surgical Sciences Division, Department of Surgery, School of Medicine, University of Maryland, Baltimore, MD.
Program in Transplantation, University of Maryland Medical System, Baltimore, MD.
Transplantation. 2023 Oct 1;107(10):2143-2154. doi: 10.1097/TP.0000000000004542. Epub 2023 Feb 23.
Solid organ transplantation saves thousands of lives suffering from end-stage diseases. Although early transplants experienced acute organ injury, medical breakthroughs, such as tissue typing, and use of immunosuppressive agents have considerably improved graft survival. However, the overall incidence of allograft injury and chronic rejection remains high. Often the clinical manifestations of organ injury or rejection are nonspecific and late. Current requirement for successful organ transplantation is the identification of reliable, accurate, disease-specific, noninvasive methods for the early diagnosis of graft injury or rejection. Development of noninvasive techniques is important to allow routine follow-ups without the discomfort and risks associated with a graft biopsy. Multiple biofluids have been successfully tested for the presence of potential proteomic biomarkers; these include serum, plasma, urine, and whole blood. Kidney transplant research has provided significant evidence to the potential of proteomics-based biomarkers for acute and chronic kidney rejection, delayed graft function, early detection of declining allograft health. Multiple proteins have been implicated as biomarkers; however, recent observations implicate the use of similar canonical pathways and biofunctions associated with graft injury/rejection with altered proteins as potential biomarkers. Unfortunately, the current biomarker studies lack high sensitivity and specificity, adding to the complexity of their utility in the clinical space. In this review, we first describe the high-throughput proteomics technologies and then discuss the outcomes of proteomics profiling studies in the transplantation of several organs. Existing literature provides hope that novel biomarkers will emerge from ongoing efforts and guide physicians in delivering specific therapies to prolong graft survival.
实体器官移植挽救了成千上万患有终末期疾病的生命。尽管早期移植会出现急性器官损伤，但诸如组织配型和使用免疫抑制剂等医学突破已显著提高了移植物的存活率。然而，同种异体移植物损伤和慢性排斥反应的总体发生率仍然很高。器官损伤或排斥反应的临床表现通常是非特异性的且出现较晚。当前成功进行器官移植的要求是识别可靠、准确、疾病特异性的非侵入性方法，用于早期诊断移植物损伤或排斥反应。开发非侵入性技术对于实现常规随访至关重要，这样可以避免与移植活检相关的不适和风险。多种生物流体已成功检测出潜在的蛋白质组学生物标志物；这些包括血清、血浆、尿液和全血。肾移植研究为基于蛋白质组学的生物标志物在急性和慢性肾排斥反应、移植肾功能延迟、早期检测移植物健康状况下降方面的潜力提供了重要证据。多种蛋白质已被认为是生物标志物；然而，最近的观察结果表明，使用与移植物损伤/排斥反应相关的类似经典途径和生物功能以及蛋白质改变作为潜在生物标志物。不幸的是，目前的生物标志物研究缺乏高灵敏度和特异性，这增加了它们在临床应用中的复杂性。在本综述中，我们首先描述高通量蛋白质组学技术，然后讨论蛋白质组学分析研究在几种器官移植中的结果。现有文献表明，持续的努力有望产生新的生物标志物，并指导医生提供特定疗法以延长移植物存活时间。
