Université Paris Descartes, Paris, France.
Am J Transplant. 2010 Mar;10(3):681-6. doi: 10.1111/j.1600-6143.2009.02968.x. Epub 2010 Feb 1.
Persistence of donor-specific anti-HLA antibodies (DSA) associated with antibody-mediated graft injuries following kidney transplantation predicts evolution toward chronic humoral rejection and reduced graft survival. Targeting plasma cells, the main antibody-producing cells, with the proteasome inhibitor bortezomib may be a promising desensitization strategy. We evaluated the in vivo efficacy of one cycle of bortezomib (1.3 mg/m(2)x 4 doses), used as the sole desensitization therapy, in four renal transplant recipients experiencing subacute antibody-mediated rejection with persisting DSA (>2000 [Mean Fluorescence Intensity] MFI). Bortezomib treatment did not significantly decrease DSA MFI within the 150-day posttreatment period in any patient. In addition, antivirus (HBV, VZV and HSV) antibody levels remained stable following treatment suggesting a lack of efficacy on long-lived plasma cells. In conclusion, one cycle of bortezomib alone does not decrease DSA levels in sensitized kidney transplant recipients in the time period studied. These results underscore the need to evaluate this new desensitization agent properly in prospective, randomized and well-controlled studies.
供者特异性抗 HLA 抗体（DSA）的持续存在与肾移植后抗体介导的移植物损伤相关，可预测慢性体液性排斥反应的进展和移植物存活率降低。针对浆细胞（主要的抗体产生细胞）的蛋白酶体抑制剂硼替佐米可能是一种有前途的脱敏策略。我们评估了硼替佐米（1.3 mg/m2 x 4 剂）一个疗程作为唯一脱敏治疗，在 4 例发生持续性 DSA（>2000 [Mean Fluorescence Intensity] MFI）的亚急性抗体介导排斥反应的肾移植受者中的体内疗效。在任何患者中，硼替佐米治疗在 150 天的治疗后期间内均未显著降低 DSA MFI。此外，抗病毒（HBV、VZV 和 HSV）抗体水平在治疗后保持稳定，提示对长寿浆细胞缺乏疗效。总之，在研究期间，硼替佐米一个疗程并不能降低致敏肾移植受者的 DSA 水平。这些结果强调需要在前瞻性、随机和对照良好的研究中对这种新的脱敏剂进行适当评估。
