Al Meshari K, Pall A, Elgamal H, Alzayer F, Altalhi M
King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Clin Transpl. 2010:383-90.
Antibody-mediated rejection (AMR) is a well-known complication of kidney transplantation. Its incidence is higher in HLA and ABO incompatible transplant recipients and in patients who develop de novo HLA antibodies. Different clinical and histological phenotypes of HLA-related AMR have been described with variable responses to conventional AMR treatment (Plasmapheresis, IVIG, thymoglobulin (ATG), and anti-CD20 antibodies). Regardless of the phenotype, once the HLA primed B cells have differentiated into antibody producing long-lived plasma cells, they become less vulnerable to conventional AMR treatment. Bortezomib (Velcade) is a proteasome inhibitor approved by the FDA for the treatment of multiple myeloma. It targets mature plasma cells, and hence it is intriguing to study its role in the suppression of long-lived plasma cells. Several previous reports have suggested effectiveness of Bortezomib in the treatment of AMR. We report our experience with Bortezomib as an adjuvant to conventional therapy in five distinct phenotypes of AMR: early acute AMR in the context of desensitization; subclinical acute AMR in the context of desensitization; late acute AMR due to de novo HLA antibody; late ACR and acute AMR due to de novo HLA antibody and chronic AMR due to de novo HLA antibody.
抗体介导的排斥反应（AMR）是肾移植中一种众所周知的并发症。其在HLA和ABO不相容的移植受者以及产生新生HLA抗体的患者中发生率更高。已经描述了HLA相关AMR的不同临床和组织学表型，对传统AMR治疗（血浆置换、静脉注射免疫球蛋白、抗胸腺细胞球蛋白（ATG）和抗CD20抗体）的反应各不相同。无论表型如何，一旦HLA致敏的B细胞分化为产生抗体的长寿浆细胞，它们就变得对传统AMR治疗不那么敏感。硼替佐米（万珂）是一种经美国食品药品监督管理局批准用于治疗多发性骨髓瘤的蛋白酶体抑制剂。它靶向成熟浆细胞，因此研究其在抑制长寿浆细胞中的作用很有意义。先前的几份报告表明硼替佐米在治疗AMR方面有效。我们报告了硼替佐米作为传统疗法辅助药物治疗五种不同表型AMR的经验：脱敏背景下的早期急性AMR；脱敏背景下的亚临床急性AMR；新生HLA抗体导致的晚期急性AMR；新生HLA抗体导致的晚期抗体介导的慢性排斥反应和急性AMR以及新生HLA抗体导致的慢性AMR。
