Kanmaz Turan, Fechner John J H, Torrealba Jose, Kim Hyoung Tae, Dong Yinchen, Oberley Terry D, Schultz Jacqueline M, Bloom Debra D, Katayama Masaaki, Dar Wasim, Markovits Judit, Schuler Walter, Hu Huaizhong, Hamawy Majed M, Knechtle Stuart J
Department of Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA.
Transplantation. 2004 Mar 27;77(6):914-20. doi: 10.1097/01.tp.0000116392.72152.75.
This study assesses the safety and efficacy of the novel human anti-human CD154 monoclonal antibody ABI793 in rhesus monkeys.
Outbred rhesus monkeys were used for renal transplantation from major histocompatibility complex-mismatched donors. Seven recipients were treated with ABI793, and six untreated recipients were used as controls. Graft function was monitored by urine output, serum creatinine, and renal biopsy. Phenotypic analysis of peripheral blood lymphocytes and mixed lymphocyte reaction were performed before transplantation and periodically after transplantation. Anti-donor major histocompatibility complex class I antibody levels were measured at the time of sacrifice.
Monkeys in the treated group demonstrated prolonged graft survival compared with controls. One monkey was sacrificed because of a urine leak on postoperative day 13. Three monkeys were sacrificed because of acute rejection (days 44, 149, and 158). Two monkeys were sacrificed because of chronic active rejection (days 154 and 221). One monkey was sacrificed on day 139 without rejection to observe the effects of ABI793 in the absence of rejection. There were no obvious clinical side effects of ABI793, but microscopic thromboembolic changes were observed in two monkeys. Lymphocyte subsets remained unaltered in all monkeys. Mixed lymphocyte reaction showed nonspecific suppression 6 weeks after transplantation. The monkeys with chronic active rejection showed relatively strong alloantibody responses.
ABI793 induces prolonged renal allograft survival in rhesus monkeys. Nevertheless, thromboembolic complications may occur and chronic allograft nephropathy may develop after anti-CD154 treatment is discontinued.
本研究评估新型人抗人CD154单克隆抗体ABI793在恒河猴中的安全性和有效性。
选用远交系恒河猴进行主要组织相容性复合体不匹配供体的肾移植。7只受体接受ABI793治疗，6只未治疗的受体作为对照。通过尿量、血清肌酐和肾活检监测移植肾功能。在移植前和移植后定期进行外周血淋巴细胞的表型分析和混合淋巴细胞反应。在处死时测量抗供体主要组织相容性复合体I类抗体水平。
与对照组相比，治疗组的猴子移植肾存活时间延长。1只猴子因术后第13天出现尿漏而被处死。3只猴子因急性排斥反应（第44、149和158天）被处死。2只猴子因慢性活动性排斥反应（第154和221天）被处死。1只猴子在第139天无排斥反应时被处死，以观察ABI793在无排斥反应情况下的作用。ABI793没有明显的临床副作用，但在2只猴子中观察到微观血栓栓塞变化。所有猴子的淋巴细胞亚群均保持不变。混合淋巴细胞反应在移植后6周显示非特异性抑制。患有慢性活动性排斥反应的猴子表现出相对较强的同种抗体反应。
ABI793可延长恒河猴肾移植的存活时间。然而，停用抗CD154治疗后可能会发生血栓栓塞并发症，并且可能会发展为慢性移植肾肾病。
