Schwaiger Elisabeth, Regele Heinz, Wahrmann Markus, Werzowa Johannes, Haidbauer Bettina, Schmidt Alice, Böhmig Georg A
Division of Nephrology and Dialysis, Department of Medicine ll, Medical University Vienna, Vienna, Austria.
Clin Transpl. 2010:391-6.
We report on a patient with chronic C4d-positive antibody-mediated rejection, who was subjected to treatment with bortezomib. Despite initial treatment with CD20 antibody rituximab and intravenous immunoglobulin, the patient presented with a steady increase in serum creatinine and de novo proteinuria. In an effort to directly target alloantibody-producing plasma cells and to prevent ongoing antibody-mediated graft injury, we applied treatment with a single cycle of bortezomib combined with dexamethasone. Treatment was associated with a > 50% decrease in DSA levels and disappearance of capillary C4d staining as detected in a follow-up biopsy. However, there were still profound glomerulitis, an unchanged degree of transplant glomerulopathy and a persistent discrete infiltration of the interstitium by CD138+ plasma cells. The clinical course was unfavorable: despite some decrease in urinary protein excretion, a further deterioration of kidney allograft function was noted. In summary, this case suggests distinct antihumoral efficacy of bortezomib also in the context of chronic AMR. Nevertheless, a major observation was that treatment failed to prevent deterioration of graft function. We speculate that, despite modulation of (complement-activating) DSA, advanced irreversible tissue injury in this late stage of rejection may have precluded a relevant clinical response. Together with other case studies, our results may provide a valuable basis for prospective trials designed to evaluate the efficacy of bortezomib in the prevention and treatment of earlier stages of chronic AMR, e.g. based on the results of early (protocol) biopsies and/or early post-transplant antibody monitoring.
我们报告了一例慢性C4d阳性抗体介导的排斥反应患者，该患者接受了硼替佐米治疗。尽管最初使用了CD20抗体利妥昔单抗和静脉注射免疫球蛋白进行治疗，但患者的血清肌酐持续升高，并出现了新发蛋白尿。为了直接靶向产生同种抗体的浆细胞并防止持续的抗体介导的移植物损伤，我们应用了单周期硼替佐米联合地塞米松进行治疗。在后续活检中发现，治疗后DSA水平下降超过50%，毛细血管C4d染色消失。然而，仍存在严重的肾小球炎，移植性肾小球病程度未变，间质中CD138 +浆细胞持续存在离散性浸润。临床病程不利：尽管尿蛋白排泄有所减少，但同种异体肾移植功能仍进一步恶化。总之，该病例表明硼替佐米在慢性抗体介导的排斥反应中也具有明显的抗体液疗效。然而，一个主要观察结果是治疗未能阻止移植功能的恶化。我们推测，尽管（补体激活）DSA得到了调节，但在排斥反应的这个晚期，晚期不可逆组织损伤可能已排除了相关的临床反应。与其他病例研究一起，我们的结果可能为前瞻性试验提供有价值的基础，这些试验旨在评估硼替佐米在预防和治疗慢性抗体介导的排斥反应早期阶段的疗效，例如基于早期（方案）活检和/或移植后早期抗体监测的结果。
