Wahrmann Markus, Haidinger Michael, Drach Johannes, Geyeregger René, Kikić Zeljko, Raab Romana, Säemann Marcus D, Böhmig Georg A
Division of Nephrology and Dialysis, Department of Medicine II, Medical University of Vienna, Vienna, Austria.
Clin Transpl. 2009:415-20.
The proteasome inhibitor bortezomib was recently shown to effectively downregulate donor-specific humoral alloimmunity in rejecting kidney transplant recipients. The anti-humoral efficiency of proteasome inhibition in wait-listed non-immunosuppressed high risk patients is less well established. This pilot study, which included two pre-sensitized hemodialysis patients, was designed to get first insights into the impact of bortezomib treatment on allosensitization. Treatment consistent in two subsequent cycles of bortezomib. In an effort to increase responsiveness to treatment the second cycle was combined with dexamethasone. During a half-year follow-up, levels of CDC-PRA reactivity slightly decreased (patient 1: 87% to 80%, patient 2: 35% to 13%). However, proportions and MFI levels of detected Luminex SA reactivities (patient 1: N = 74; patient 2: N = 22) were not affected in a meaningful way. In parallel, bortezbmib treatment had no considerable effect on total immunoglobulin and kappa/lambda light chain levels. Our data suggest that, in absence of basal immunosuppression or rejection therapy, bortezomib may not or only modestly affect levels of humoral allosensitization. Future studies will have to clarify if additional anti-humoral measures or intensified treatment enhance the efficiency of proteasome inhibition as a desensitization strategy in advance of transplantation.
蛋白酶体抑制剂硼替佐米最近被证明可有效下调正在接受肾移植排斥反应的患者的供体特异性体液同种免疫。蛋白酶体抑制在等待名单上的未接受免疫抑制的高危患者中的抗体液效率尚未得到充分证实。这项包括两名预先致敏的血液透析患者的初步研究旨在初步了解硼替佐米治疗对同种致敏的影响。治疗采用两个连续周期的硼替佐米。为了提高对治疗的反应性，第二个周期联合了地塞米松。在半年的随访期间，补体依赖细胞毒试验（CDC-PRA）反应性水平略有下降（患者1：从87%降至80%，患者2：从35%降至13%）。然而，检测到的Luminex SA反应性的比例和平均荧光强度（MFI）水平（患者1：N = 74；患者2：N = 22）没有受到有意义的影响。同时，硼替佐米治疗对总免疫球蛋白和κ/λ轻链水平没有显著影响。我们的数据表明，在没有基础免疫抑制或抗排斥治疗的情况下，硼替佐米可能不会或只会适度影响体液同种致敏水平。未来的研究将必须阐明，在移植前，额外的抗体液措施或强化治疗是否会提高蛋白酶体抑制作为一种脱敏策略的效率。
