Genberg H, Hansson A, Wernerson A, Wennberg L, Tydén G
Division of Transplantation Surgery, Karolinska Institute Karolinska University Hospital, Huddinge, Sweden.
Am J Transplant. 2006 Oct;6(10):2418-28. doi: 10.1111/j.1600-6143.2006.01497.x. Epub 2006 Aug 21.
The anti-CD20 antibody rituximab has recently gained interest as a B-cell depleting agent in renal transplantation. However, little is known about the pharmacodynamics of rituximab in renal transplant recipients. We have therefore studied the effect of single-dose rituximab in combination with conventional triple immunosuppressive therapy on the B-cell population in peripheral blood as well as in tissues. A total of 49 renal transplant recipients received single-dose rituximab, as induction therapy (n = 36) or as anti-rejection therapy (n = 13). We counted B cells in peripheral blood and performed immunohistochemical staining on lymph nodes and kidney transplant tissue samples to assess the prevalence of B cells. In all but 6 patients (88%) complete depletion of B cells in peripheral blood was achieved. In adults, 15 months after treatment the CD19+ and CD20+ cell counts were still below 5 cells/muL in the majority of patients (78%). The immunohistochemical staining showed a complete elimination of B cells in kidney tissue and a reduction of B cells in lymph nodes. In conclusion, single-dose rituximab in kidney transplant recipients evokes a long-term elimination of B cells in peripheral blood as well as within the kidney transplant. The effect seems to extend beyond the expected 3-12 months observed in lymphoma patients.
抗CD20抗体利妥昔单抗最近作为一种肾移植中的B细胞清除剂受到关注。然而，关于利妥昔单抗在肾移植受者中的药效学知之甚少。因此，我们研究了单剂量利妥昔单抗联合传统三联免疫抑制疗法对外周血以及组织中B细胞群体的影响。共有49名肾移植受者接受了单剂量利妥昔单抗治疗，其中作为诱导治疗的有36例，作为抗排斥治疗的有13例。我们对外周血中的B细胞进行计数，并对淋巴结和肾移植组织样本进行免疫组化染色，以评估B细胞的患病率。除6例患者外（88%），所有患者外周血中的B细胞均实现了完全清除。在成人中，治疗15个月后，大多数患者（78%）的CD19+和CD20+细胞计数仍低于5个/微升。免疫组化染色显示肾组织中的B细胞完全清除，淋巴结中的B细胞减少。总之，肾移植受者使用单剂量利妥昔单抗可在外周血以及肾移植内长期清除B细胞。这种效果似乎超出了淋巴瘤患者中观察到的预期3至12个月。
