Woodle E S, Walsh R C, Alloway R R, Girnita A, Brailey P
Department of Surgery, University of Cincinnati, Cincinnati, OH, USA.
Pediatr Transplant. 2011 Sep;15(6):548-56. doi: 10.1111/j.1399-3046.2011.01543.x.
AMR is being recognized with increasing efficiency, but continues to present a significant threat to renal allograft survival. Traditional therapies for AMR (IVIG, plasmapheresis, rituximab, and antilymphocyte preparations) in general have provided inconsistent results and do not deplete the source of antibody production, viz., the mature plasma cell. Recently, the first plasma cell-targeted therapy in humans has been developed using bortezomib (a first in class PI) for AMR treatment in kidney transplant recipients. Initial experience with bortezomib involved treatment of refractory AMR. Subsequently, the efficacy of bortezomib in primary therapy for AMR was demonstrated. In a multicenter collaborative effort, the initial results with bortezomib in AMR have been confirmed and expanded to pediatric and adult heart transplant recipients. More recently, results from a prospective, staged desensitization trial has shown that bortezomib alone can substantially reduce anti-HLA antibody levels. These results demonstrate the significant potential of proteasome inhibition in addressing humoral barriers. However, the major advantage of proteasome inhibition lies in the numerous potential strategies for achieving synergy.
抗菌药物耐药性（AMR）正以越来越高的效率被识别出来，但它仍然对肾移植的存活构成重大威胁。AMR的传统治疗方法（静脉注射免疫球蛋白、血浆置换、利妥昔单抗和抗淋巴细胞制剂）总体上效果不一，而且不能消除抗体产生的源头，即成熟浆细胞。最近，已开发出人类首个针对浆细胞的疗法，使用硼替佐米（一种一流的蛋白酶体抑制剂）治疗肾移植受者的AMR。硼替佐米的初步经验涉及治疗难治性AMR。随后，硼替佐米在AMR初始治疗中的疗效得到了证实。在一项多中心合作中，硼替佐米在AMR方面的初步结果得到了确认，并扩展到儿科和成人心脏移植受者。最近，一项前瞻性、分阶段脱敏试验的结果表明，单独使用硼替佐米可大幅降低抗人白细胞抗原（HLA）抗体水平。这些结果证明了蛋白酶体抑制在解决体液屏障方面的巨大潜力。然而，蛋白酶体抑制的主要优势在于实现协同作用的众多潜在策略。
