Division of Transplantation Surgery, von Liebig Transplant Center, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Transplantation. 2011 Mar 15;91(5):536-41. doi: 10.1097/TP.0b013e3182081333.
Donor specific alloantibody producing plasma cells (DSA-PCs) appear resistant to conventional immunosuppressive agents. This study aimed to determine the impact of pretransplant monotherapy with the proteasome inhibitor bortezomib on DSA-PCs in sensitized renal allograft candidates and to assess if DSA-PC depletion would enhance the efficacy of DSA removal using plasma exchange (PE).
Only patients with DSA levels considered too high to successfully undergo transplantation with PE alone were included in this study: i.e. those with a baseline B flow cytometric crossmatch (BFXM) >450 against a potential living donor.Four sensitized patients received 4 doses (1.3 mg/m/dose) of bortezomib and 4 received 16 doses. The number of DSA-PCs was determined pre and post-treatment using an ELISPOT assay. Five of these patients underwent post-treatment PE and their response was compared to 8 highly-sensitized patients (BFXM >450) who underwent PE alone.
When considering all 8 patients as one group, bortezomib treatment decreased DSA-PCs in the marrow (mean±SD=16.7±14.5 DSA-PCs/ml pre-treatment vs. 6.2±3.6 DSA-PCs/ml after treatment, P=0.048). In the time frame of the study, bortezomib alone did not decrease serum DSA levels. However, five bortezomib treated patients underwent PE and showed a greater decease in DSA compared to the historical control group of 8 sensitized patients who underwent PE alone (mean decrease in BFXM channel shift=272.6±92.1 with bortezomib vs 95.4±72.2 in PE alone P=0.008).
Bortezomib depletes DSA-PCs and appears to potentiate DSA removal by PE in sensitized renal transplant recipients.
供体特异性同种抗体产生浆细胞（DSA-PC）似乎对常规免疫抑制剂有抗性。本研究旨在确定在致敏肾移植候选者中，移植前使用蛋白酶体抑制剂硼替佐米进行单药治疗对 DSA-PC 的影响，并评估 DSA-PC 耗竭是否会增强使用血浆置换（PE）去除 DSA 的效果。
只有那些 DSA 水平被认为太高，无法单独使用 PE 成功移植的患者才被纳入本研究：即那些基线 B 流式细胞交叉配型（BFXM）>450 与潜在的活体供体。四名致敏患者接受了 4 剂（1.3mg/m/剂）硼替佐米治疗，4 名患者接受了 16 剂治疗。使用 ELISPOT 检测法在治疗前后确定 DSA-PC 的数量。其中 5 名患者接受了治疗后的 PE，将他们的反应与 8 名高度致敏患者（BFXM>450）进行了比较，这些患者仅接受了 PE 治疗。
当将所有 8 名患者作为一个组考虑时，硼替佐米治疗降低了骨髓中的 DSA-PC（治疗前平均±SD=16.7±14.5 DSA-PC/ml vs. 治疗后 6.2±3.6 DSA-PC/ml，P=0.048）。在研究期间，硼替佐米单独使用并未降低血清 DSA 水平。然而，5 名接受硼替佐米治疗的患者在接受 PE 后，与单独接受 PE 的 8 名致敏患者的历史对照组相比，DSA 下降幅度更大（BFXM 通道移位的平均下降值=272.6±92.1 硼替佐米 vs. 单独 PE 时的 95.4±72.2，P=0.008）。
硼替佐米耗竭 DSA-PC，并似乎增强了致敏肾移植受者中 PE 对 DSA 的清除作用。
