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肾移植中的耐受现状

Current status of tolerance in kidney transplantation.

作者信息

Chandran Sindhu, Feng Sandy

机构信息

aDivision of Nephrology, Department of Medicine bDivision of Transplantation, Department of Surgery, University of California San Francisco (UCSF), San Francisco, California, USA.

出版信息

Curr Opin Nephrol Hypertens. 2016 Nov;25(6):591-601. doi: 10.1097/MNH.0000000000000269.

Abstract

PURPOSE OF REVIEW

The attainment of tolerance remains a highly desirable goal in recipients of kidney transplants. Achievement of this goal would extend graft survival and eradicate toxicities related to long-term immunosuppression. Understanding mechanisms of tolerance and strategies to induce tolerance - their risk/benefit profiles - is essential for future success.

RECENT FINDINGS

Mechanistic studies of spontaneously tolerant kidney transplant recipients have uncovered potential roles for B or regulatory T cells, or both, in the maintenance of tolerance. Mixed hematopoietic chimerism has been the most commonly used approach to induce tolerance. Distinct protocols at three major transplant centers have led to successful withdrawal of immunosuppression in a subset of living donor kidney transplant recipients at the expense of complications such as infections and graft versus host disease. The addition of regulatory cell therapies to tolerance induction protocols could enhance success while minimizing complications.

SUMMARY

This review summarizes the features of spontaneous tolerance in kidney transplant recipients, the results of clinical trials of tolerance induction in the context of living donor kidney transplant, and potential measures to improve the safety and efficacy of tolerance induction strategies.

摘要

综述目的

在肾移植受者中实现免疫耐受仍是一个非常理想的目标。实现这一目标将延长移植物存活时间并消除与长期免疫抑制相关的毒性。了解免疫耐受机制以及诱导免疫耐受的策略——它们的风险/获益情况——对于未来的成功至关重要。

最新发现

对自发形成免疫耐受的肾移植受者的机制研究揭示了B细胞或调节性T细胞或两者在维持免疫耐受中的潜在作用。混合造血嵌合体一直是诱导免疫耐受最常用的方法。三个主要移植中心采用的不同方案已使一部分活体供肾移植受者成功停用免疫抑制剂,但代价是出现感染和移植物抗宿主病等并发症。在免疫耐受诱导方案中加入调节性细胞疗法可提高成功率并将并发症降至最低。

总结

本综述总结了肾移植受者自发免疫耐受的特点、活体供肾移植背景下免疫耐受诱导的临床试验结果,以及提高免疫耐受诱导策略安全性和有效性的潜在措施。

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