Comparison of polyclonal induction agents in pediatric renal transplantation
Comparison of polyclonal induction agents in pediatric renal transplantation
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多克隆诱导剂在小儿肾移植中的比较
DOI：
10.1034/j.1399-3046.2001.00054.x
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发表时间：
2001
影响因子：
1.3
通讯作者：
T. Bunchman
中科院分区：
文献类型：
--
作者：
P. Brophy;S. Thomas;K. McBryde;T. Bunchman
摘要：综合儿科数据表明，使用多克隆抗体的抗T细胞诱导治疗可改善短期和长期肾移植物存活的结局。多克隆药物，包括胸腺球蛋白（Thy），一种兔抗胸腺细胞球蛋白;明尼苏达（马）抗淋巴母细胞球蛋白（ALG）;和ATGAM，一种马抗胸腺细胞球蛋白（ATG），均抑制B和T细胞。虽然不存在特异性T细胞亚群标记物来测量多克隆诱导的免疫抑制的充分性，但流式细胞术分析已用于评价CD 3、CD 4和CD 8细胞的抑制。Thy目前正在我们中心进行儿科试验，我们在之前的儿科诱导方案中使用了ATG和ALG。ALG（20 mg/kg/天）和ATG（15 mg/kg/天）给药10天，而Thy（2 mg/kg/天）给药5天。 所有诱导均伴随术前静脉注射甲强龙（10 mg/kg），随后口服泼尼松（2 mg/kg/天），逐渐减少。 接受ALG或ATG的患者在术前（1.5 mg/kg/天）和术后（2 mg/kg/天）接受硫唑嘌呤给药。 接受Thy治疗的患者给予吗替麦考酚酯（MMF）（1200 mg/m2/d）。一旦肾功能允许（肌酐<基线的50%，尿量活跃）（通过HPLC测定谷值目标为150-250 ng/mL），则开始术后环孢素A（CsA）（14 mg/kg/天）给药（所有组）。 通过流式细胞术测定2-18岁肾移植受者的CD 3、CD 4和CD 8 T细胞值，比较诱导后2-10天内使用的多克隆诱导剂[Thy（n = 8），平均年龄9.7 ± 2.3岁; ATG（n = 13），平均年龄10.1 ± 4.1岁; ALG（n = 9），平均年龄9.3 ± 3.7岁]。 数据表示为相对于基线T细胞亚群（第1天= 100%）剩余细胞的平均百分比，因为基础T细胞亚群值存在较大的年龄差异。 流式细胞术数据表明，与ATG或ALG的10天疗程相比，5天的Thy似乎在第10天产生相等或更大的外周血T细胞抑制。
Abstract: Collective pediatric data suggest that anti‐T‐cell induction therapy with polyclonal antibodies improves the outcome of both short‐ and long‐term renal allograft survival. Polyclonal agents, including thymoglobulin (Thy), a rabbit anti‐thymocyte globulin; Minnesota (horse) anti‐lymphoblast globulin (ALG); and ATGAM, a horse anti‐thymocyte globulin (ATG), all suppress B and T cells. While no specific T‐cell subset marker exists to measure the adequacy of immunosuppression with polyclonal induction, flow cytometric analysis has been used to evaluate the suppression of CD3, CD4, and CD8 cells. Thy is currently undergoing pediatric trials at our center, and we have utilized ATG and ALG in previous pediatric induction protocols. ALG (20 mg/kg/day) and ATG (15 mg/kg/day) were administered over 10 days, whereas Thy (2 mg/kg/day) was given over 5 days. All inductions were accompanied by preoperative intravenous solumedrol (10 mg/kg) followed by oral prednisone (2 mg/kg/day) with taper. Preoperative (1.5 mg/kg/day) and post‐operative (2 mg/kg/day) azathioprine was administered to patients receiving ALG or ATG. Mycophenolate mofetil (MMF) (1200 mg/m2/day) was given to the patients receiving Thy. Post‐operative cyclosporin A (CsA) (14 mg/kg/day) was started (for all groups) once renal function permitted (creatinine < 50% of baseline with brisk urine output) (trough goal 150–250 ng/mL via HPLC). Values for CD3, CD4, and CD8 T cells were determined by flow cytometry in 2–18‐yr‐old renal transplant recipients, comparing the polyclonal induction agent utilized [Thy (n = 8), mean age 9.7 ± 2.3 yr; ATG (n = 13), mean age 10.1 ± 4.1 yr; and ALG (n = 9), mean age 9.3 ± 3.7 yr] over days 2–10 post‐induction. Data were expressed as the average percentage of cells remaining relative to the baseline T‐cell subsets (day 1 = 100%), because of the large age variation present in basal T‐cell subset values. The flow cytometric data suggest that 5 days of Thy appears to give an equal or greater peripheral blood T‐cell suppression by day 10 than a 10‐day course of either ATG or ALG.