Baron Daniel, Giral Magali, Brouard Sophie
INSERM, UMR 1064, Nantes, France.
CHU de Nantes, ITUN, Nantes, France.
Transpl Int. 2015 Aug;28(8):938-59. doi: 10.1111/tri.12578. Epub 2015 Apr 21.
In kidney transplantation, minimizing the side effects of the immunosuppressive regimen and inducing tolerance to allograft are the two main objectives to improve outcome. At present, these objectives are far from being achieved and remain elusive for the majority of transplant recipients. Rejection rate and mortality on the long term are still unacceptable. There is thus a pressing need to improve this situation. Therefore, some spontaneously tolerant kidney recipients are described in clinics, and recent advances in immunological and molecular techniques have led to a resurgence of interest in studying those rare transplanted recipients through coordinated efforts from international consortia. Indeed, they offer, on the one hand, the possibility to develop specific biomarkers indicative of this state that would constitute a major advantage in the care of the patients allowing personalized minimization of drugs, so reducing related costs and side effects. On the other hand, they represent a unique model of study to understand the mechanisms of regulation implicated in this state that may help the development of inducing therapies. Recent efforts, concentrated on noninvasive analyses of peripheral blood, identified a predominance of several B-cell subsets, some of which harbouring regulatory functions, and related marker genes. These findings, validated in independent multicentric cohorts, led credence to an unsuspected role for the B-cell compartment in tolerance to kidney allograft. The identification of patients, harbouring these markers, among immunosuppressed recipients with stable graft function and the existence of drugs with selective effect on B cell pave the way for the possibility to improve long-term graft outcomes. Therefore, before routine application, these findings need to be confirmed in large prospective studies in the context of planned reduced immunosuppression.
在肾移植中，将免疫抑制方案的副作用降至最低并诱导对同种异体移植物的耐受性是改善移植效果的两个主要目标。目前，这些目标远未实现，对于大多数移植受者来说仍然难以捉摸。长期的排斥率和死亡率仍然不可接受。因此，迫切需要改善这种状况。因此，临床上描述了一些自发耐受的肾移植受者，并且免疫和分子技术的最新进展使得国际联盟通过协同努力，对研究这些罕见的移植受者重新产生了兴趣。事实上，一方面，它们提供了开发指示这种状态的特定生物标志物的可能性，这将在患者护理中构成一个主要优势，允许个性化地减少药物使用，从而降低相关成本和副作用。另一方面，它们代表了一个独特的研究模型，以了解这种状态下涉及的调节机制，这可能有助于诱导治疗的发展。最近的研究集中在外周血的非侵入性分析上，发现了几种B细胞亚群占主导地位，其中一些具有调节功能，以及相关的标记基因。这些发现在独立的多中心队列中得到验证，使人们相信B细胞区室在肾移植耐受中具有意想不到的作用。在具有稳定移植物功能的免疫抑制受者中识别出携带这些标志物的患者，以及存在对B细胞有选择性作用的药物，为改善长期移植物结果创造了可能性。因此，在常规应用之前，这些发现需要在计划减少免疫抑制的背景下进行的大型前瞻性研究中得到证实。
