Bieber C P, Griepp R B, Oyer P E, Wong J, Stinson E B
Transplantation. 1976 Nov;22(5):478-88. doi: 10.1097/00007890-197611000-00011.
Serum rabbit globulin (RG) clearance rates were determined in 30 consecutive cardiac transplant recipients by radioimmune assay of serum RG levels after completion of an initial postoperative course of rabbit anti-human antithymocyte globulin (RATG). Twenty patients, who exhibited rapid RG elimination rates (average half-life, 1.6 days), had a rejection onset time of 16.2 days rejection frequency of 3.9 episodes/100 patient days, and a 1-year survival rate of 59%, respectively, as compared with 28.3 days, 1.9 episodes/100 patient days, and 80%, respectively, for the 10 patients with more prolonged initial RG elimination rates (average half-life, 11.4 days); Nineteen patients received one or more repeat courses of RATG. In 16 of these a progressive increase in RG half-life during subsequent RATG administration could be demonstrated. A close correlation was observed between total RATG doses given in the initial course and peak serum levels of RG obtained (r = 0.82) and between onset of rejection and initial t1/2 RG (r = 0.69). This latter correlation was improved by the elimination of one of the 30 patients (r = 0.81) or by considering only those patients treated from a single RATG batch (r = 0.85; n = 15). No significant relationship was detected between any of the parameters assayed and (1) total RATG dose, or (2) rosette inhibition titers of RATG administered. Survival and rejection parameters of the first 30 patients receiving RATG were compared with the previous 20 receiving equine antithymocyte globulin; these 50 comprising the entire population in which rejection was confirmed by cardiac biopsy. Rejection onset was 20 versus 12 days, rejection frequency was 3.1 versus 5.0 episodes/100 patient days, and graft survival at 1 year was 66 versus 41% for the RATG-equine antithymocyte globulin-treated patients, respectively. From these data it was concluded that (1) RATG administration favorably affects transplantation outcome; (2) RATG half-life, as reflected by RG clearance rates, was the most important variable governing RATG effectiveness, (3) variation in rosette inhibition titers within RATG batches made in the same fashion from large rabbit pools were of minimal clinical importance; and (4) monitoring of serum RG levels provided a necessary and rational basis for effective modulation of immunosuppressive therapy.
通过放射免疫分析法测定血清兔球蛋白（RG）水平，对30例连续心脏移植受者在完成兔抗人抗胸腺细胞球蛋白（RATG）术后初始疗程后进行血清兔球蛋白（RG）清除率测定。20例患者，其RG清除率较快（平均半衰期1.6天），排斥反应开始时间为16.2天，排斥反应频率为3.9次/100患者日，1年生存率分别为59%；相比之下，10例初始RG清除率较长（平均半衰期11.4天）的患者，其排斥反应开始时间分别为28.3天，排斥反应频率为1.9次/100患者日，1年生存率为80%。19例患者接受了一个或多个RATG重复疗程。其中16例在后续RATG给药期间可证明RG半衰期逐渐增加。观察到初始疗程中给予的RATG总剂量与获得的RG血清峰值水平之间密切相关（r = 0.82），以及排斥反应开始与初始RG半衰期之间密切相关（r = 0.69）。排除30例患者中的1例后（r = 0.81）或仅考虑来自单个RATG批次治疗的患者（r = 0.85；n = 15），后一种相关性得到改善。在所检测的任何参数与（1）RATG总剂量或（2）所给予RATG的玫瑰花结抑制效价之间均未检测到显著关系。将接受RATG的前30例患者的生存和排斥参数与先前接受马抗胸腺细胞球蛋白的20例患者进行比较；这50例患者构成了通过心脏活检确诊有排斥反应的全部人群。对于接受RATG - 马抗胸腺细胞球蛋白治疗的患者，排斥反应开始时间分别为20天和12天，排斥反应频率分别为3.1次/100患者日和5.0次/100患者日，1年移植物存活率分别为66%和41%。从这些数据得出结论：（1）给予RATG对移植结果有有利影响；（2）如RG清除率所反映的RATG半衰期是决定RATG有效性的最重要变量；（3）以相同方式从大量兔群制备的RATG批次内玫瑰花结抑制效价的变化在临床上重要性最小；（4）监测血清RG水平为有效调节免疫抑制治疗提供了必要且合理的依据。
