Nephrology and Transplantation Department, CHU Henri Mondor, APHP, Créteil, France; Unité Inserm U955, équipe 21 and CIC Biothérapies 504, CHU Henri Mondor, APHP, Paris XII University, Créteil, France.
Am J Transplant. 2014 May;14(5):1173-82. doi: 10.1111/ajt.12721. Epub 2014 Apr 14.
Phase III clinical studies have shown that kidney transplant (KT) recipients treated with the costimulation blocker belatacept exhibited a better renal allograft function and lower donor-specific anti-HLA immunization when compared to recipients treated with calcineurin inhibitors (CNI). We analyzed B cell phenotype in KT recipients treated with belatacept and stable renal function (N = 13). Results were compared to those observed in stable patients treated with CNI (N = 12), or with chronic antibody-mediated rejection (N = 5). Both transcriptional profile and phenotypic characterization of peripheral B cells were performed by real-time polymerase chain reaction and flow cytometry, respectively. In belatacept group, the frequency and absolute number of transitional B cells as defined by both phenotypes: CD19(+) CD24(hi) CD38(hi) and CD19(+) IgD(hi) CD38(hi) CD27(-) , as well as naïve B cells were significantly higher compared with CNI group. B cell activating factor (BAFF) and BAFF receptor mRNA levels were significantly lower in belatacept group than in CNI group. These results show for the first time that belatacept influences B cell compartment by favoring the occurrence of transitional B cells with potential regulatory properties, as described in operational tolerant patients. This role may explain the lower alloimmunization rate observed in belatacept-treated patients.
III 期临床试验表明，与接受钙调磷酸酶抑制剂 (CNI) 治疗的肾移植 (KT) 受者相比，接受共刺激阻断剂贝利尤单抗治疗的肾移植受者具有更好的肾移植功能和更低的供体特异性抗 HLA 免疫。我们分析了接受贝利尤单抗治疗且肾功能稳定 (N = 13) 的 KT 受者的 B 细胞表型。结果与接受 CNI 治疗的稳定患者 (N = 12) 或慢性抗体介导排斥反应患者 (N = 5) 进行了比较。通过实时聚合酶链反应和流式细胞术分别对外周 B 细胞的转录谱和表型特征进行了分析。在贝利尤单抗组中，两种表型定义的过渡 B 细胞的频率和绝对数量：CD19(+) CD24(hi) CD38(hi) 和 CD19(+) IgD(hi) CD38(hi) CD27(-)，以及幼稚 B 细胞均显著高于 CNI 组。贝利尤单抗组的 B 细胞激活因子 (BAFF) 和 BAFF 受体 mRNA 水平明显低于 CNI 组。这些结果首次表明，贝利尤单抗通过促进具有潜在调节特性的过渡 B 细胞的发生来影响 B 细胞区室，这在操作性耐受患者中已有描述。这种作用可能解释了贝利尤单抗治疗患者中观察到的较低同种免疫率。
