国产重组抗CD25人源化单克隆抗体在肾移植免疫诱导中的应用研究

Application research of domestic recombinant humanized anti-CD25 monoclonal antibody in immunity induction of renal transplantation

目的研究国产重组抗CD25人源化单克隆抗体(健尼哌)在肾移植免疫诱导应用中的有效性和安全性。方法本前瞻性研究对象选取2011年5月至2012年5月在中山大学附属第一医院器官移植中心接受初次亲属活体供肾肾移植患者共20例,随机分为实验组和对照组。实验组10例,免疫诱导给予2剂健尼哌(每剂75 mg,术中1剂、术后14 d 1剂);对照组10例,免疫诱导给予2剂巴利昔单抗(每剂20 mg,术中1剂、术后4 d 1剂)。密切随访,观察两组患者术后急性排斥反应、移植物功能延迟恢复(DGF)、感染等并发症的发生率,记录患者和移植肾的存活情况。分别于术前、术后1 d、术后3 d、术后7 d、术后14 d、术后1个月、术后3个月以及术后6个月,检测两组患者的血清肌酐、血尿素氮、外周血白细胞计数、淋巴细胞比例等实验室检测指标,比较两组间差别。分别于上述各时间点抽取患者外周静脉血2 ml,采用流式细胞仪分析两组患者调节性T细胞比例(Treg%)的变化。结果随访期间,两组患者均无死亡病例。实验组和对照组各有1例患者出现急性排斥反应,经甲泼尼龙冲击治疗及抗胸腺细胞球蛋白(ATG)治疗后,肾功能均恢复至正常。两组患者的急性排斥反应、上呼吸道感染、肺部感染、尿路感染、白细胞减少、血小板减少及DGF等并发症发生率比较,差异无统计学意义(均为P>0.05)。在各时间点上,两组患者的血清肌酐、血尿素氮、外周血白细胞计数、淋巴细胞比例比较,差异均无统计学意义(均为P>0.05)。两组患者Treg%的变化基本相似,均在术后1个月内维持较低水平,术后3个月逐渐回升,至术后6个月接近或回复到术前水平。在术前、术后3 d的时间点,两组患者的Treg%差异无统计学意义(均为P>0.05);而在术后1 d、7 d、14 d及1个月的时间点,实验组的Treg%均高于对照组,差异有统计学意义(均为P<0.05);在术后3个月、6个月的时间点,实验组的Treg%均低于对照组,差异亦有统计学意义(均为P<0.05)。结论在肾移植免疫诱导应用中,健尼哌具有和国外同类产品相似的有效性及安全性。

Objective To study the effect and safety of domestic recombinant humanized anti-CD25 monoclonal antibody （Jian Nipai） in immunity induction of renal transplantation. Methods Twenty primary recipients, who underwent living-related donor renal transplantation in the Organ Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University from May 2011 to May 2012, were enrolled in this prospective study. The patients were randomly divided into two groups： experimental group and control group. Ten patients in experimental group were given two doses of Jian Nipai for immunity induction （75 mg/dose, 1 dose during the operation and 1 dose on the 14th d after operation）, while 10 patients in control group were given two doses of basiliximab （20 mg/dose, 1 dose during the operation and 1 dose on the 4^th d after operation）. The follow-up was conducted strictly and the incidence of complications such as postoperative acute rejection, delayed graft function （ DGF）, infection was observed. The survival of the recipients and kidney graft were recorded. The laboratory test indexes of patients in two groups such as serum creatinine, blood urea nitrogen, white blood cell count and proportion of lymphocyte were detected at the time points of pre-operation, 1 d, 3 d, 7 d, 14 d, 1 month, 3 months, 6 months after operation and the difference was compared between two groups. The peripheral venous blood of the patients （2 ml） was taken at the time points mentioned above and the changes of regulatory T cells percentage （ Treg% ） in patients of two groups was analyzed by flow cytometer. Results There was no death case in two groups during follow-up period. One case in experimental group and one in control group suffered acute rejection, and their renal function returned to normal level after impulse therapy of methylprednisolone and antithymocyte globulin. There were no significant differences in the incidences of complications such as acute rejection, upper respiratory infection, pulmonary infection, urinary tract infection, leucopenia, thrombocytopenia and DGF between two groups （ all in P 〉 0. 05 ）. There were no significant differences in the serum creatinine, blood urea nitrogen, white blood cell count and proportion of lymphocyte between two groups at every time point （ all in P 〉 0. 05 ）. The changes of Treg% in two groups were similar. The Treg% at one month after operation stayed at a low level and began to rise at 3 months after operation and returned （or closely ） to the preoperative level at 6 months after operation. There was no significant difference in the Treg% between two groups at the time points of pre-operation and 3 d after operation （ all in P 〉 0. 05 ）. Treg% in experimental group was significantly higher than that in control group at the time points of 1 d, 7 d, 14 d and one month after operation （all in P 〈0. 05）. Treg% in experimental group was significantly lower than that in control group at the time points of 3 months and 6 months after operation （all in P 〈 0. 05 ）. Conclusions Jian Nipai has the same effect and safety as the similar drug abroad in the immunity induction of renal transplantation.