Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu postreconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST Research Study of ATG and Rituximab in Renal Transplantation was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit antithymocyte globulin and rituximab and initiated immunosuppression (IS) withdrawal (ISW) at 26 weeks. The primary endpoint was freedom from rejection at 52 weeks post-ISW. Six of the 10 subjects successfully completed ISW. Of these 6 subjects, 4 restarted immunosuppressive medications due to acute rejection or recurrent disease, 1 remains IS-free for over 9 years, and 1 was lost to follow-up after being IS-free for 42 weeks. There were no cases of patient or graft loss. CD19 B cell frequencies returned to predepletion levels by 26 weeks posttransplant; immunoglobulin DCD27-naïve B cells predominated. In contrast, memory cells dominated the repopulation of the T cell compartment. A regimen of combined B and T cell depletion did not generate the tolerogenic B cell profile observed in preclinical studies and did not lead to durable tolerance in the majority of kidney transplant recipients.

中文翻译：

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抗胸腺细胞球蛋白和利妥昔单抗诱导后活体肾移植受者的免疫抑制戒断：前瞻性临床试验的结果

肾移植受者的持久耐受仍然是一个重要但难以实现的目标。我们假设将 B 细胞去除与 T 细胞去除相结合，会产生由未成熟过渡 B 细胞主导的重建后免疫环境，有利于耐受。肾移植中 ATG 和利妥昔单抗的免疫耐受网络 ITN039ST 研究是一项针对活体肾移植受者的前瞻性多中心试点研究，这些受者接受兔抗胸腺细胞球蛋白和利妥昔单抗诱导，并在 26 周时开始免疫抑制 (IS) 戒断 (ISW)。主要终点是 ISW 后 52 周无排斥反应。 10 名受试者中有 6 名成功完成 ISW。在这 6 名受试者中，4 名因急性排斥反应或疾病复发而重新开始使用免疫抑制药物，1 名未出现 IS 超过 9 年，1 名在 42 周未出现 IS 后失访。没有患者或移植物丢失的病例。移植后 26 周，CD19 B 细胞频率恢复至耗尽前水平；免疫球蛋白 DCD27 未接触过的 B 细胞占主导地位。相比之下，记忆细胞主导了 T 细胞区室的重新增殖。联合去除 B 细胞和 T 细胞的方案并没有产生临床前研究中观察到的耐受性 B 细胞特征，也没有在大多数肾移植受者中产生持久的耐受性。