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用抗白细胞介素-2受体单克隆抗体预防急性排斥反应。II. 第二次肾移植后的结果。

Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. II. Results after a second kidney transplantation.

作者信息

Hourmant M, Le Mauff B, Cantarovich D, Dantal J, Baatard R, Denis M, Jacques Y, Karam G, Soulillou J P

机构信息

Service de Néphrologie et Immunologie Clinique, Unité INSERM U.211, Laboratoire de Biochimie, Centre Hospitalier et Universitaire de Nantes, France.

出版信息

Transplantation. 1994 Jan;57(2):204-7. doi: 10.1097/00007890-199401001-00008.

Abstract

The focus of progress in transplantation immunosuppression is to achieve more specific immunosuppression with monoclonal antibodies. We have already shown that the efficacy of 33B3.1, a rat monoclonal Ig2A directed against the human IL-2 receptor, was similar to that of rabbit antithymocyte globulin in the prevention of acute rejection in first kidney transplants. A similar comparative analysis has been made in 40-sec renal transplants. ATG (1 mg/kg/day) or 33B3.1 (10 mg/day) was administered during the first 10 days postgrafting in association with corticosteroids and azathioprine. Cyclosporine was introduced on day 9 and azathioprine/CsA constituted the patient's maintenance treatment after day 45. Rejection treatment consisted of equine antilymphocyte globulin in both cases and of steroid boluses when patients were under Cyclosporine. One patient in each group died. Graft survival was 90%, 85%, and 79% in the ATG group (n = 20) and 100%, 89%, and 89% in the 33B3.1 group (n = 20) at 3, 12, and 24 months, respectively. Of the ATG group patients, 45% and 40% in the 33B3.1 group had at least one rejection episode, half the episodes in the MoAb cohort occurring under 33B3.1, vs. none in the ATG group. Transplant function was similar in both groups. Viral infections appeared to be more frequent with ATG (60%) than with 33B3.1 (12%), with CMV accounting for half of these in the ATG group, and none in the MoAb group. Tolerance of both agents was good. Of the 33B3.1 recipients, 70% developed anti-33B3.1 antibodies. From these data, we conclude that this anti-IL-2 receptor MoAb seems less effective than rabbit ATG as induction treatment in second kidney transplant patients.

摘要

移植免疫抑制的进展重点在于利用单克隆抗体实现更具特异性的免疫抑制。我们已经表明,33B3.1(一种针对人白细胞介素-2受体的大鼠单克隆Ig2A)在预防首次肾移植急性排斥反应方面的疗效与兔抗胸腺细胞球蛋白相似。在40例肾移植中进行了类似的比较分析。在移植后的前10天,联合使用皮质类固醇和硫唑嘌呤给予抗胸腺细胞球蛋白(ATG,1毫克/千克/天)或33B3.1(10毫克/天)。在第9天开始使用环孢素,45天后硫唑嘌呤/环孢素构成患者的维持治疗。在两种情况下,排斥反应的治疗均包括马抗淋巴细胞球蛋白,当患者使用环孢素时还包括大剂量类固醇。每组各有1例患者死亡。在第3、12和24个月时,ATG组(n = 20)的移植肾存活率分别为90%、85%和79%,33B3.1组(n = 20)分别为100%、89%和89%。ATG组患者中有45%至少发生一次排斥反应,33B3.1组为40%,单克隆抗体队列中一半的排斥反应发生在33B3.1治疗期间,而ATG组无此情况。两组的移植肾功能相似。ATG组(60%)的病毒感染似乎比33B3.1组(12%)更频繁,其中巨细胞病毒在ATG组占这些感染的一半,而单克隆抗体组无感染。两种药物的耐受性都良好。33B3.1治疗的患者中,70%产生了抗33B3.1抗体。从这些数据我们得出结论,在第二次肾移植患者中,作为诱导治疗,这种抗白细胞介素-2受体单克隆抗体似乎不如兔抗胸腺细胞球蛋白有效。

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