Horn Edward T, Xu Qingyong, Dibridge Julie N, Huston Jessica H, Hickey Gavin W, Kaczorowski David J, Keebler Mary E, Zeevi Adriana
University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Clin Transplant. 2023 Dec;37(12):e15132. doi: 10.1111/ctr.15132. Epub 2023 Sep 13.
In this project, we describe proteasome inhibitor (PI) treatment of antibody-mediated rejection (AMR) in heart transplantation (HTX). From January 2018 to September 2021, 10 patients were treated with PI for AMR: carfilzomib (CFZ) n = 8; bortezomib (BTZ) n = 2. Patients received 1-3 cycles of PI. All patients had ≥1 strong donor-specific antibody (DSA) (mean fluorescence intensity [MFI] > 8000) in undiluted serum. Most DSAs (20/21) had HLA class II specificity. The MFI of strong DSAs had a median reduction of 56% (IQR = 13%-89%) in undiluted serum and 92% (IQR = 53%-95%) at 1:16 dilution. Seventeen DSAs in seven patients were reduced > 50% at 1:16 dilution after treatment. Four DSAs from three patients did not respond. DSA with MFI > 8000 at 1:16 dilution was less responsive to treatment. 60% (6/10) patients presented with graft dysfunction; 4/6 recovered ejection fraction > 40% after treatment. Pathologic AMR was resolved in 5/7 (71.4%) of patients within 1 year after treatment. 9/10 (90%) patients survived to 1 year after AMR diagnosis. Using PI in AMR resulted in significant DSA reduction with some resolution of graft dysfunction. Larger studies are needed to evaluate PI for AMR.
在本项目中，我们描述了蛋白酶体抑制剂（PI）治疗心脏移植（HTX）中抗体介导的排斥反应（AMR）的情况。2018年1月至2021年9月，10例患者接受PI治疗AMR：卡非佐米（CFZ）n = 8；硼替佐米（BTZ）n = 2。患者接受1 - 3个周期的PI治疗。所有患者未稀释血清中均有≥1种强供体特异性抗体（DSA）（平均荧光强度[MFI] > 8000）。大多数DSA（20/21）具有HLA II类特异性。未稀释血清中强DSA的MFI中位数降低了56%（四分位间距[IQR] = 13% - 89%），在1:16稀释时降低了92%（IQR = 53% - 95%）。治疗后，7例患者中的17种DSA在1:16稀释时降低> 50%。3例患者的4种DSA无反应。1:16稀释时MFI > 8000的DSA对治疗反应较差。60%（6/10）的患者出现移植物功能障碍；4/6的患者治疗后射血分数恢复> 40%。5/7（71.4%）的患者在治疗后1年内病理AMR得到缓解。9/10（90%）的患者在AMR诊断后存活至1年。在AMR中使用PI可显著降低DSA，并使移植物功能障碍得到一定程度的缓解。需要更大规模的研究来评估PI治疗AMR的效果。
