早期和晚期急性抗体介导的排斥反应在免疫学上不同，并且对蛋白酶体抑制的反应也不同。

Early and late acute antibody-mediated rejection differ immunologically and in response to proteasome inhibition.

机构信息

Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0558, USA.

出版信息

Transplantation. 2011 Jun 15;91(11):1218-26. doi: 10.1097/TP.0b013e318218e901.

DOI:10.1097/TP.0b013e318218e901

PMID:21617586

Abstract

BACKGROUND

The efficacy of plasma cell targeted therapies for antibody-mediated rejection (AMR) has not been defined in detail. The purpose of this study was to compare early and late acute AMR in terms of immunologic characteristics and responses with proteasome inhibitor (PI) therapy.

METHODS

Renal transplant recipients with acute AMR were treated with PI-based regimens. Early acute AMR was defined as occurring within 6 months posttransplant. Immunodominant donor-specific antibody (iDSA) was defined as the DSA with the highest level.

RESULTS

Results are expressed as early or late acute AMR. Thirty AMR episodes (13 early, 17 late) were treated in 12 and 16 patients. Early but not late AMR was associated with presensitization. Late AMR iDSA levels were higher, and specificities were primarily class II (DQ being most frequent). Early AMR patients demonstrated greater reduction in iDSA at 7, 14, and 30 days and at the posttreatment nadir (81.5%+21.2% vs. 51.4%+27.6%; P<0.01). Early AMR patients were more likely to demonstrate histologic resolution/improvement (87.5% vs. 53.8%; P=0.13). Both groups demonstrated significant improvement in renal function.

CONCLUSIONS

Early and late AMR exhibit distinct immunologic characteristics and respond differently to PI therapy.

摘要

背景

针对抗体介导排斥反应（AMR）的浆细胞靶向治疗的疗效尚未详细确定。本研究的目的是比较蛋白酶体抑制剂（PI）治疗时早期和晚期急性 AMR 的免疫特征和反应。

方法

接受 PI 为基础的方案治疗急性 AMR 的肾移植受者。早期急性 AMR 定义为移植后 6 个月内发生。免疫优势供体特异性抗体（iDSA）定义为水平最高的 DSA。

结果

结果表示为早期或晚期急性 AMR。12 例和 16 例患者共治疗了 30 次 AMR 发作（13 次早期，17 次晚期）。早期 AMR 与致敏有关，但晚期 AMR 则没有。晚期 AMR 的 iDSA 水平更高，特异性主要为 II 类（DQ 最常见）。早期 AMR 患者在第 7、14 和 30 天以及治疗后最低点时 iDSA 的减少更为显著（81.5%+21.2%比 51.4%+27.6%；P<0.01）。早期 AMR 患者更有可能表现出组织学缓解/改善（87.5%比 53.8%；P=0.13）。两组患者的肾功能均有显著改善。