高剂量静脉注射免疫球蛋白疗法用于治疗伴有急性和慢性移植物功能障碍的肾移植受者的供体特异性抗体。

High dose intravenous immunoglobulin therapy for donor-specific antibodies in kidney transplant recipients with acute and chronic graft dysfunction.

作者信息

Cooper James E, Gralla Jane, Klem Patrick, Chan Laurence, Wiseman Alexander C

机构信息

1 Division of Renal Diseases and Hypertension, Transplant Center, University of Colorado Denver, CO. 2 Department of Pediatrics, University of Colorado Denver, CO. 3 Department of Pharmacy, University of Colorado Denver, CO. 4 Address correspondence to: James E. Cooper, Transplant Center, University of Colorado Denver, Mail Stop F749, AOP 7089, 1635 North Aurora Court, Aurora, CO 80045.

出版信息

Transplantation. 2014 Jun 27;97(12):1253-9. doi: 10.1097/01.TP.0000443226.74584.03.

DOI:10.1097/01.TP.0000443226.74584.03

PMID:24937199

Abstract

BACKGROUND

Postkidney transplant donor-specific antibodies (DSA) have been identified as important contributors to graft loss. Few therapeutic options exist and have been met with limited success. We report outcomes in patients with de novo DSA and graft damage treated with a protocol of high-dose intravenous immunoglobulin (IVIG).

METHODS

Retrospective analysis of 28 kidney transplant recipients with de novo DSA and graft damage in the form of either chronic graft dysfunction (group 1, n=20) or a recent previous acute antibody-mediated rejection (AMR) episode (group 2, n=8) prescribed a standard regimen of high-dose (5 g/kg) IVIG dosed over 6 months.

RESULTS

Mean fluorescence intensity (MFI) of 70 total DSA decreased by 12%at the end of treatment (T1, P=0.14) and by 18%at last follow up (T2, P=0.035) compared with treatment initiation (T0) MFI. The most robust effect was seen in class I DSA (37% decrease at T2 versus T0, P=0.05) and in DSA from patients in group 2 (52% decrease at T2 versus T0, P=0.008). Graft function stabilized in patients in group 2 but continued to decline in those in group 1.

CONCLUSION

High-dose IVIG resulted in modest DSA MFI reductions in patients with previous graft damage, with a larger effect occurring in class I DSA in patients with a previous acute AMR. There was no clinical treatment benefit in patients with ongoing chronic graft damage, whereas high-dose IVIG may reduce the risk of chronic graft dysfunction in those with an acute AMR event.

摘要

背景

肾移植术后供者特异性抗体（DSA）已被确认为导致移植肾丢失的重要因素。目前治疗选择较少，且效果有限。我们报告了采用大剂量静脉注射免疫球蛋白（IVIG）方案治疗的新发DSA和移植肾损伤患者的治疗结果。

方法

回顾性分析28例肾移植受者，这些患者存在新发DSA且伴有移植肾损伤，表现为慢性移植肾功能不全（第1组，n = 20）或近期发生过急性抗体介导的排斥反应（AMR）（第2组，n = 8），均接受了为期6个月的标准大剂量（5 g/kg）IVIG治疗方案。

结果

与治疗开始时（T0）的平均荧光强度（MFI）相比，70种DSA的总MFI在治疗结束时（T1）下降了12%（P = 0.14），在最后一次随访时（T2）下降了18%（P = 0.035）。I类DSA的下降最为明显（T2时比T0下降37%，P = 0.05），第2组患者的DSA下降也很明显（T2时比T0下降52%，P = 0.008）。第2组患者的移植肾功能稳定，而第1组患者的移植肾功能继续下降。