THE HUMORAL IMMUNE-RESPONSE IN HUMANS FOLLOWING CROSS-PERFUSION OF PORCINE ORGANS
THE HUMORAL IMMUNE-RESPONSE IN HUMANS FOLLOWING CROSS-PERFUSION OF PORCINE ORGANS
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DOI：
10.1097/00007890-199510270-00017
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发表时间：
1995-10-27
期刊：
影响因子：
6.2
通讯作者：
PLATT, JL
中科院分区：
文献类型：
--
作者：
COTTERELL, AH;COLLINS, BH;PLATT, JL
异种移植中的一个主要问题是异种器官移植到免疫抑制受体后发生的体液反应的性质，因为这种反应可能介导移植物的延迟型损伤。为了开始解决这个问题，我们的特点的变化发生在患者暴露于模拟移植条件下的猪器官的异种反应性抗体的性质。在两名患者的血液已经交叉灌注通过猪肝作为治疗肝衰竭，异种反应性IgM的滴度增加了4倍，异种反应性IgG的滴度增加了60倍灌注程序后10天内。异种反应性IgM和IgG抗体对Gal α 1-3Gal具有特异性，这是基于与表达该决定子的猪内皮细胞和牛甲状腺球蛋白的结合，以及在用α-半乳糖苷酶处理猪内皮细胞或牛甲状腺球蛋白后结合减少。依次添加到内皮细胞的血清量饱和抗体结合位点之前和10天后获得的猪器官灌注显示，没有增加以上的水平与血清灌注前观察到的IgM结合，这表明新的决定因素没有确定。此外，在猪器官灌注前和灌注后10天获得的血清中IgM与猪内皮细胞结合的功能亲合力没有变化，即使在以后的时间，也没有检测到新引发的针对猪主动脉内皮细胞靶标的抗体的存在。因此，暴露于血管化器官中的猪抗原导致异种反应性IgM和IgG抗体水平的增加，然而，这些抗体表现出与天然抗体相似的性质。
A major question in xenotransplantation is the nature of the humoral response that would occur following the transplantation of a xenogeneic organ into an immunosuppressed recipient as such a response could mediate delayed types of injury to the graft. To begin to address this issue we characterized the changes in the properties of xenoreactive antibodies occurring in patients exposed to porcine organs under conditions simulating transplantation. In two patients whose blood had been cross-perfused through porcine livers as a treatment for hepatic failure, the titer of xenoreactive IgM increased by four-fold and the titer of xenoreactive IgG increased by sixty-fold within ten days after perfusion procedures. The xenoreactive IgM and IgG antibodies were specific for Gal alpha 1-3Gal based on binding to porcine endothelial cells and bovine thyroglobulin, which express this determinant, and on the decrease in binding following treatment of porcine endothelial cells or bovine thyroglobulin with alpha-galactosidase. The sequential addition to endothelial cells of amounts of serum known to saturate antibody-binding sites obtained before and ten days after perfusion of porcine organs revealed no increase in binding of IgM above the level observed with serum obtained before perfusion, suggesting that new determinants were not identified. Moreover, the functional avidity of binding to porcine endothelial cells of IgM in serum obtained before and ten days after perfusion of porcine organs was unchanged, Even at later times, the presence of newly elicited antibodies against porcine aortic endothelial cell targets was not detected. Thus, exposure to porcine antigens in a vascularized organ results in increases in the levels of xenoreactive IgM and IgG antibodies-however, these antibodies exhibit properties similar to natural antibodies.