Morales J, Bono M R, Fierro A, Iñiguez R, Zehnder C, Rosemblatt M, Calabran L, Herzog C, Benavente D, Aguiló J, Pefaur J, Alba A, Ferrario M, Simon W, Contreras L, Buckel E
Centro de Trasplante, Clínica Las Condes, Laboratoric de Inmunologia, Facutad de Ciencìas, Universidad Andrés Bello and Fundación Ciencìa para la Vida, Santiago, Santiago, Chile.
Transplant Proc. 2008 Nov;40(9):3223-8. doi: 10.1016/j.transproceed.2008.03.066.
Alemtuzumab (ALT), a humanized monoclonal anti-CD52 antibody, was introduced in solid organ transplantation as an induction agent. ALT associated with anticalcineurins has provided a low incidence of acute rejection episodes (ARE) and potential tolerogenic properties. We analyzed the clinical outcomes and effects on peripheral Treg of renal transplant recipients treated with ALT. Six-month data on kidney alone or kidney combined with pancreas or liver patients treated with ALT and tacrolimus (TAC) in standard doses were compared with those on renal transplant recipients of similar demography who were not treated with ALT. We evaluated patient and graft survivals, ARE incidence, hematological parameters, renal function, adverse events, and CD4+CD25+FoxP3+ T cells in peripheral blood. Demographics of recipients, donors, and transplants were similar in both groups. Mean HLA mismatch was slightly greater among ALT-treated patients (3.5 vs 2.5). No combined transplantation was performed in the ALT-untreated group. Patient and graft survivals were 100% without rejection or serious infections in both groups. ALT-treated recipients showed anemia and leukopenia in 3 patients as well as severe lymphopenia in 5 recipients, who partially recovered on day 90. Final mean plasma creatinine was 1.4 mg/dL, while calculated creatinine clearance was approximately 65 mL/min in both groups. Mean Treg cell percentage was higher among ALT-treated recipients than the comparative group or healthy controls (P < .05). In conclusion, renal transplantation results obtained using ALT with rigorous immunosuppressive therapy were excellent; serious adverse events and acute rejection were absent. The effect of the increased proportion of Treg cells must be evaluated with longer observation.
阿仑单抗(ALT)是一种人源化抗CD52单克隆抗体,作为一种诱导剂被引入实体器官移植领域。与抗钙调神经磷酸酶联合使用的ALT导致急性排斥反应(ARE)的发生率较低,并具有潜在的致耐受性特性。我们分析了接受ALT治疗的肾移植受者的临床结局以及对其外周调节性T细胞(Treg)的影响。将单独肾移植或肾联合胰腺或肝移植且接受标准剂量ALT和他克莫司(TAC)治疗患者的6个月数据,与未接受ALT治疗、人口统计学特征相似的肾移植受者的数据进行比较。我们评估了患者和移植物的存活率、ARE发生率、血液学参数、肾功能、不良事件以及外周血中的CD4 + CD25 + FoxP3 + T细胞。两组受者、供者和移植情况的人口统计学特征相似。接受ALT治疗的患者平均HLA错配率略高(3.5对2.5)。未接受ALT治疗的组未进行联合移植。两组患者和移植物存活率均为100%,无排斥反应或严重感染。接受ALT治疗的受者中有3例出现贫血和白细胞减少,5例出现严重淋巴细胞减少,这些情况在第90天时部分恢复。两组最终的平均血浆肌酐均为1.4 mg/dL,计算得出的肌酐清除率约为65 mL/min。接受ALT治疗的受者中Treg细胞的平均百分比高于对照组或健康对照组(P <.05)。总之,使用ALT并进行严格免疫抑制治疗所获得的肾移植结果非常理想;未出现严重不良事件和急性排斥反应。Treg细胞比例增加的影响必须通过更长时间的观察来评估。