Prolongation of primate cardiac allograft survival by treatment with ANTI-CD40 ligand (CD154) antibody.
Prolongation of primate cardiac allograft survival by treatment with ANTI-CD40 ligand (CD154) antibody.
复制标题
通过 ANTI-CD40 配体 (CD154) 抗体治疗延长灵长类同种异体心脏移植物的存活。
DOI：
10.1097/00007890-199912150-00026
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发表时间：
1999
期刊：
影响因子：
6.2
通讯作者：
Miller,GG
中科院分区：
文献类型：
--
作者：
Pierson3rd,RN;Chang,AC;Blum,MG;Blair,KS;Scott,MA;Atkinson,JB;Collins,BJ;Zhang,JP;Thomas,DW;Burkly,LC;Miller,GG
背景。我们评估了人源化抗cd154抗体（hu5c8）是否延长了灵长类动物同种异体心脏移植的存活时间。方法：在MHC ii型错配的食蟹猴之间进行异位心脏移植。比较围手术期给药hu5c8组（1组，n= 6）、持续给药hu5c8组（2组，n= 3）和对照组（n= 4）的生存率。结果：1组移植体中位生存期为49天（14 ~ 56天），2组为106天（56 ~ 245天），对照组为5天（5 ~ 6天）（所有比较均P< 0.05）。在收缩性稳定的hu5c8处理的移植物中经常出现淋巴细胞浸润。供体特异性混合淋巴细胞反应一般保存。血管炎和细胞内膜增生在排斥移植物中普遍存在，但在2组发生较晚，发生率较低。抗cd154抗体可显著延长灵长类动物同种异体心脏移植的存活时间，且耐受性良好。持续剂量的hu5c8可提高生存率，并可能与较低的血管病理发生率相关。我们得出结论，hu5c8治疗是抑制灵长类动物心脏移植急性排斥反应的有效途径。
Background.We evaluated whether a humanized anti-CD154 antibody (hu5c8) prolongs primate cardiac allograft survival.Methods.Heterotopic cardiac allografts were performed between MHC class II-mismatched cynomolgus monkeys. Survival was compared between groups treated with a perioperative dosing of hu5c8 (group 1; n= 6), sustained dosing with hu5c8 (group 2; n= 3), and control regimens (n= 4). All recipients received fresh donor-specific transfusions during surgery.Results.Median graft survival was 49 days (range 14 to 56) in group 1 and 106 days (range 56 to 245) in group 2, compared with 5 days (range 5 to 6) for controls (P< 0.05 for all comparisons). Lymphocytic infiltrates were often present in hu5c8-treated grafts with stable contractility. Donor-specific mixed lymphocyte reaction was generally preserved. Vasculitis and cellular intimal proliferation were prevalent in rejected grafts but occurred later and were less prevalent in group 2.Conclusions.Anti-CD154 antibody markedly prolongs the survival of cardiac allografts in primates and is well tolerated. Sustained dosing with hu5c8 yielded improved survival and may be associated with a lower incidence of vascular pathology. We conclude that hu5c8 therapy is an effective approach for inhibiting acute cardiac allograft rejection in primates.