Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Transplantation. 2010 Jun 15;89(11):1385-90. doi: 10.1097/TP.0b013e3181d9e1c0.
Recipient presensitization represents a major hurdle to successful renal transplantation. Previous case series have suggested that the proteasome inhibitor bortezomib directly affects the alloantibody-secreting plasma cells in rejecting allograft recipients. However, the ability of this agent to desensitize nonimmunosuppressed transplant candidates before transplantation is currently unknown.
In this analysis, two sensitized hemodialysis patients were selected to receive two subsequent bortezomib cycles. Bortezomib was given at 1.3 mg/m(2) on days 1, 4, 8, and 11. Dexamethasone was added to the second cycle to enhance treatment efficiency. Serial immune monitoring included cytotoxic panel reactive antibody testing, Luminex single antigen testing for anti-human leukocyte antigen (HLA) IgG with or without C4d-fixing capability, and ABO antibody detection.
During a half-year follow-up period, cytotoxic panel reactive antibody decreased from 87% to 80% (patient 1) and 37% to 13% (patient 2). Patient 1 showed a 40% reduction in binding intensities of identified Luminex HLA single antigen reactivities and, in parallel, slight reductions in ABO blood group antibody and total immunoglobulin levels. In patient 2, bortezomib did not affect circulating antibody levels in a meaningful way. Both patients showed a more than 50% reduction in the levels of anti-HLA antibody-triggered C4d deposition to Luminex beads.
Our initial experience suggests that, without additional immunosuppressive measures, bortezomib has modest effects on circulating antibodies against HLA or blood group antigens. The reduced levels of antibody-triggered complement fixation, however, imply potential clinical relevance of proteasome inhibition for recipient desensitization.
受者致敏是成功进行肾移植的主要障碍。先前的病例系列研究表明，蛋白酶体抑制剂硼替佐米直接影响排斥同种异体移植物受者的同种抗体分泌浆细胞。然而，目前尚不清楚该药物在移植前是否具有使未免疫抑制的移植候选者脱敏的能力。
在这项分析中，选择了两名致敏的血液透析患者接受两次后续的硼替佐米周期。硼替佐米在第 1、4、8 和 11 天以 1.3mg/m(2)的剂量给药。在第二个周期中添加地塞米松以提高治疗效率。连续的免疫监测包括细胞毒性面板反应性抗体检测、Luminex 单抗原检测抗人类白细胞抗原（HLA）IgG 与或不与 C4d 结合能力、以及 ABO 抗体检测。
在半年的随访期间，细胞毒性面板反应性抗体从 87%降至 80%（患者 1）和 37%降至 13%（患者 2）。患者 1 显示出识别的 Luminex HLA 单抗原反应的结合强度降低了 40%，并且 ABO 血型抗体和总免疫球蛋白水平也略有降低。在患者 2 中，硼替佐米对循环抗体水平没有产生有意义的影响。两名患者显示出抗 HLA 抗体触发的 C4d 沉积到 Luminex 珠的水平降低了 50%以上。
我们的初步经验表明，在没有额外免疫抑制措施的情况下，硼替佐米对针对 HLA 或血型抗原的循环抗体有适度的影响。然而，抗体触发补体固定水平的降低意味着蛋白酶体抑制对受者脱敏具有潜在的临床相关性。
