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肺移植中抗体介导性排斥反应管理的当前挑战与机遇

Current challenges and opportunities in the management of antibody-mediated rejection in lung transplantation.

作者信息

Hulbert Amanda L, Pavlisko Elizabeth N, Palmer Scott M

机构信息

Department of Pharmacy.

Department of Pathology.

出版信息

Curr Opin Organ Transplant. 2018 Jun;23(3):308-315. doi: 10.1097/MOT.0000000000000537.

DOI:10.1097/MOT.0000000000000537
PMID:29742565
Abstract

PURPOSE OF REVIEW

There is increasing recognition of the importance of antibody-mediated rejection (AMR) after lung transplantation. The development of donor-specific antibodies, a key feature of AMR, occurs in approximately 30% of lung transplant recipients and is associated with poor posttransplant outcomes. This review highlights recently developed AMR diagnostic criteria in lung transplantation, potential mechanisms that mediate the development of AMR, and discusses current and emerging treatment strategies for this significant, graft-limiting complication.

RECENT FINDINGS

A major advance is the development of consensus guidelines to precisely define AMR amongst lung transplant. Regimens for the treatment of AMR continue to evolve with varying success reported with regards to antibody clearance and improving clinical outcomes. A multimodality treatment approach is common, typically involving a combination of intravenous immune globulin, plasmapheresis, rituximab, and bortezomib or carfilzomib. Recent studies suggest several new agents including tocilizumab, belimumab, daratumumab, plerixafor, and C1 esterase inhibitor as potentially novel and effective therapies to employ in AMR treatment.

SUMMARY

Despite advancements in the diagnosis of AMR through well defined consensus guidelines, there is limited evidence to guide treatment. Current data suggests that conventional approaches are of suboptimal efficacy, but emerging therapeutic agents with diverse biological mechanisms offer promise for improved AMR treatment.

摘要

综述目的

肺移植后抗体介导的排斥反应(AMR)的重要性日益受到认可。供体特异性抗体的产生是AMR的一个关键特征,约30%的肺移植受者会出现这种情况,且与移植后不良预后相关。本综述重点介绍了肺移植中最近制定的AMR诊断标准、介导AMR发生的潜在机制,并讨论了针对这种严重的、限制移植物存活的并发症的当前及新兴治疗策略。

最新发现

一项重大进展是制定了共识指南,以精确界定肺移植中的AMR。AMR的治疗方案不断演变,在抗体清除和改善临床结局方面取得了不同程度的成功。多模式治疗方法较为常见,通常包括静脉注射免疫球蛋白、血浆置换、利妥昔单抗以及硼替佐米或卡非佐米的联合应用。最近的研究表明,几种新药包括托珠单抗、贝利尤单抗、达雷妥尤单抗、普乐沙福和C1酯酶抑制剂可能是AMR治疗中新颖有效的疗法。

总结

尽管通过明确的共识指南在AMR诊断方面取得了进展,但指导治疗的证据有限。目前的数据表明,传统方法疗效欠佳,但具有不同生物学机制的新兴治疗药物有望改善AMR的治疗效果。

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