Zarkhin V, Li L, Kambham N, Sigdel T, Salvatierra O, Sarwal M M
Department of Pediatrics, Stanford University Medical Center, Stanford, CA, USA.
Am J Transplant. 2008 Dec;8(12):2607-17. doi: 10.1111/j.1600-6143.2008.02411.x. Epub 2008 Sep 18.
We report 1-year outcomes of a randomized study of Rituximab versus standard-of-care immunosuppression (Thymoglobulin and/or pulse steroids) for treatment of biopsy confirmed, acute transplant rejection with B-cell infiltrates, in 20 consecutive recipients (2-23 years). Graft biopsies, with Banff and CADI scores, CD20 and C4d stains, were performed at rejection and 1 and 6 months later. Peripheral blood CMV, EBV and BK viral loads, graft function, DSA, immunoglobulins, serum humanized antichimeric antibody (HACA) and Rituximab, and lymphocyte counts were monitored until 1 year posttreatment. Rituximab infusions were given with a high index of safety without HACA development and increased infections complications. Rituximab therapy resulted in complete tissue B-cell depletion and rapid peripheral B-cell depletion. Peripheral CD19 cells recovered at a mean time of approximately 12 months. There were some benefits for the recovery of graft function (p = 0.026) and improvement of biopsy rejection scores at both the 1- (p = 0.0003) and 6-month (p < 0.0001) follow-up biopsies. Reappearance of C4d deposition was not seen on follow-up biopsies after Rituximab therapy, but was seen in 30% of control patients. There was no change in DSA in either group, independent of rejection resolution. This study reports safety and suggests further investigation of Rituximab as an adjunctive treatment for B-cell-mediated graft rejection.
我们报告了一项随机研究的1年结果，该研究对比了利妥昔单抗与标准免疫抑制治疗（抗胸腺细胞球蛋白和/或冲击剂量类固醇）用于治疗经活检证实的、伴有B细胞浸润的急性移植排斥反应，研究对象为20名连续的接受者（年龄2至23岁）。在发生排斥反应时以及之后1个月和6个月时进行移植肾活检，评估Banff和CADI评分，进行CD20和C4d染色。监测外周血巨细胞病毒、EB病毒和BK病毒载量、移植肾功能、供者特异性抗体、免疫球蛋白、血清人源化抗嵌合抗体（HACA）和利妥昔单抗水平以及淋巴细胞计数，直至治疗后1年。利妥昔单抗输注具有较高的安全性，未出现HACA，感染并发症也未增加。利妥昔单抗治疗导致组织中B细胞完全耗竭以及外周B细胞迅速耗竭。外周CD19细胞平均在约12个月时恢复。在1个月（p = 0.0003）和6个月（p < 0.0001）的随访活检中，利妥昔单抗治疗在移植肾功能恢复（p = 0.026）和活检排斥反应评分改善方面有一定益处。利妥昔单抗治疗后的随访活检未发现C4d沉积再现，但在30%的对照患者中可见。两组的供者特异性抗体均无变化，与排斥反应的缓解无关。本研究报告了利妥昔单抗的安全性，并建议进一步研究其作为B细胞介导的移植排斥反应辅助治疗的作用。
