Massart A, Ghisdal L, Abramowicz M, Abramowicz D
Department of Nephrology, Dialysis, and Transplantation, CUB Hôpital Erasme and Institute of Interdisciplinary Research in Molecular and Human Biology (IRIBHM), Université Libre de Bruxelles, Brussels, Belgium.
Department of Nephrology, Centre Hospitalier EpiCURA, Baudour, Belgium.
Clin Exp Immunol. 2017 Aug;189(2):138-157. doi: 10.1111/cei.12981. Epub 2017 May 29.
In the 1960s, our predecessors won a historical battle against acute rejection and ensured that transplantation became a common life-saving treatment. In parallel with this success, or perhaps because of it, we lost the battle for long-lived transplants, being overwhelmed with chronic immune insults and the toxicities of immunosuppression. It is likely that current powerful treatments block acute rejection, but at the same time condemn the few circulating donor cells that would have been able to elicit immunoregulatory host responses towards the allograft. Under these conditions, spontaneously tolerant kidney recipients - i.e. patients who maintain allograft function in the absence of immunosuppression - are merely accidents; they are scarce, mysterious and precious. Several teams pursue the goal of finding a biomarker that would guide us towards the 'just right' level of immunosuppression that avoids rejection while leaving some space for donor immune cells. Some cellular assays are attractive because they are antigen-specific, and provide a comprehensive view of immune responses toward the graft. These seem to closely follow patient regulatory capacities. However, these tests are cumbersome, and require abundant cellular material from both donor and recipient. The latest newcomers, non-antigen-specific recipient blood transcriptomic biomarkers, offer the promise that a practicable and simple signature may be found that overcomes the complexity of a system in which an infinite number of individual cell combinations can lead possibly to graft acceptance. Biomarker studies are as much an objective - identifying tolerant patients, enabling tolerance trials - as a means to deciphering the underlying mechanisms of one of the most important current issues in transplantation.
20世纪60年代，我们的前辈在抗击急性排斥反应的战斗中赢得了历史性胜利，确保移植成为一种常见的挽救生命的治疗方法。与这一成功并行，或者也许正是因为这一成功，我们在争取长期存活移植的战斗中失利，被慢性免疫损伤和免疫抑制的毒性所困扰。目前强大的治疗方法可能会阻断急性排斥反应，但同时也会使少数能够引发宿主对同种异体移植物产生免疫调节反应的循环供体细胞受到抑制。在这种情况下，自发耐受的肾移植受者——即在没有免疫抑制的情况下维持同种异体移植物功能的患者——只是偶然情况；他们稀少、神秘且珍贵。几个研究团队致力于寻找一种生物标志物，以指导我们达到“恰到好处”的免疫抑制水平，既能避免排斥反应，又能为供体免疫细胞留出一些空间。一些细胞检测方法很有吸引力，因为它们具有抗原特异性，能全面反映对移植物的免疫反应。这些检测似乎与患者的调节能力密切相关。然而，这些检测方法很繁琐，需要供体和受体提供大量细胞材料。最新出现的非抗原特异性受体血液转录组生物标志物有望找到一种可行且简单的特征，从而克服一个系统的复杂性，在这个系统中，无数种单个细胞组合可能导致移植物被接受。生物标志物研究既是一个目标——识别耐受患者，开展耐受试验——也是一种手段，用于解读移植领域当前最重要问题之一的潜在机制。
