Le Mauff B, Hourmant M, Rougier J P, Hirn M, Dantal J, Baatard R, Cantarovich D, Jacques Y, Soulillou J P
Service de Néphrologie et d'Immunologie Clinique, C.H.R.U. Nantes, France.
Transplantation. 1991 Aug;52(2):291-6. doi: 10.1097/00007890-199108000-00020.
A murine IgG1 monoclonal antibody, 25-3 (Immunotech, France), directed against the alpha chain (CD11a) of the human LFA1 molecule was used in the treatment of 7 histologically documented first acute rejection in first kidney transplantations under cyclosporine. Four patients (group I) received 20 mg/day for 2 days and 10 mg/day for 8 days of 25-3 MoAb. One developed Quincke's edema after the first injection of 25-3 and was immediately withdrawn from the study. In 2 patients, whose serum creatinine continued to increase, 25-3 MoAb was replaced by steroids, followed by ALG after 3 and 4 days of treatment, respectively. In the last case, rejection was reversed by 25-3 MoAb alone. As the clinical response of rejection to 25-3 was poor, another group of 3 patients (group II) was treated with 25-3 at a dose of 40 mg/day for 2 days, 20 mg/day for 2 days, and 10 mg/day for 6 days, but 25-3 was still unsuccessful in reversing acute rejection, and rescue treatment was initiated between days 5 and 8 in all cases. MoAb tolerance was excellent in 3 patients. With the exception of the one case of Quincke's edema, only minor side effects were noted in the last 3 recipients. 25-3 MoAb serum trough levels peaked between 1.5-3.5 micrograms/ml at day 3 in group I and between 2-9 micrograms/L at day 2 in group II. Surprisingly, only one patient, in group I, exhibited a borderline IgG immune response against 25-3. These findings suggest that the 25-3 anti-CD11a MoAb is ineffective in controlling the course of acute rejection in kidney transplantation. However as already reported for another anti-LFA1 or with an anti-CD4 MoAb in mouse, 25-3 would be the first example in humans of a MoAb that does not elicit a strong immune response against its own determinants. This property might have important applications if 25-3 can prevent rejection in a prophylactic protocol or block the immune response against other MoAbs.
一种针对人淋巴细胞功能相关抗原1（LFA1）分子α链（CD11a）的鼠源IgG1单克隆抗体25 - 3（法国免疫技术公司生产）被用于治疗7例经组织学证实的首次肾移植术后急性排斥反应，这些患者在环孢素治疗下接受首次肾移植。4例患者（I组）接受25 - 3单克隆抗体治疗，剂量为20毫克/天，共2天，之后为10毫克/天，共8天。1例患者在首次注射25 - 3后出现昆克水肿，立即退出研究。2例患者血清肌酐持续升高，25 - 3单克隆抗体被类固醇替代，分别在治疗3天和4天后给予抗淋巴细胞球蛋白（ALG）。在最后1例患者中，单独使用25 - 3单克隆抗体逆转了排斥反应。由于25 - 3对排斥反应的临床疗效不佳，另一组3例患者（II组）接受25 - 3治疗，剂量为40毫克/天，共2天，20毫克/天，共2天，10毫克/天，共6天，但25 - 3仍未能成功逆转急性排斥反应，所有病例均在第5至8天开始采取挽救治疗。3例患者对单克隆抗体耐受性良好。除1例昆克水肿病例外，最后3例接受治疗者仅出现轻微副作用。I组患者在第3天25 - 3单克隆抗体血清谷浓度峰值在1.5 - 3.5微克/毫升之间，II组患者在第2天峰值在2 - 9微克/升之间。令人惊讶的是，I组中仅1例患者对25 - 3表现出临界IgG免疫反应。这些发现表明，25 - 3抗CD11a单克隆抗体在控制肾移植急性排斥反应进程方面无效。然而，正如之前在小鼠中针对另一种抗LFA1或抗CD4单克隆抗体所报道的那样，25 - 3将是人类中首个不会引发针对自身决定簇强烈免疫反应的单克隆抗体实例。如果25 - 3能够在预防性方案中预防排斥反应或阻断针对其他单克隆抗体的免疫反应，这一特性可能具有重要应用价值。
