我们报道了一项随机研究的1年期结果,该研究主要用于比较利妥昔单抗和标准免疫抑制方案(ATG和/或激素)治疗20例连续活检证实的B细胞浸润的急性排斥反应的儿童肾移植受者的结果。在发生排斥反应以及移植后1年、6年时行移植肾的活检,进行Banff和CADI评分、CD20和C4d的染色。移植后1年内监测患者外周血CMV、EBV和BK病毒当量、移植物功能、DSA结果、免疫球蛋白、血清人化抗嵌合抗体(HACA)和利妥昔单抗、淋巴细胞计数。利妥昔单抗的输注其安全指数较高,并未产生HACA以及感染并发症的升高。利妥昔治疗能够导致组织B细胞的完全清除并能快速清除外周血的B细胞。外周血CD19细胞平均需要12个月才能恢复。患者移植肾功能有所恢复(p = 0.026)且在随访1个月和六个月活检能够改善活检排斥反应的评分(p = 0.0003和p < 0.0001)。利妥昔单抗治疗中未发现C4d沉积的复现,但是在对照组中有30%患者出现复现。两组DSA均为有所改变。该研究提示了使用利妥昔单抗的安全性,并提示我们需要关于采用利妥昔单抗辅助治疗B细胞介导的排斥反应的进一步研究。
Zarkhin V, Li L, Kambham N, Sigdel T, Salvatierra O, Sarwal MM. Department of Pediatrics, Stanford University Medical Center, Stanford, CA, USA.
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. |