Utility of xenografts: Lack of correlation between PRA and natural antibodies to swine
Utility of xenografts: Lack of correlation between PRA and natural antibodies to swine
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DOI：
10.1111/j.1399-3089.1997.tb00162.x
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发表时间：
1997-02-01
影响因子：
3.9
通讯作者：
Cosimi, A
中科院分区：
文献类型：
--
作者：
Bartholomew, A;Latinne, D;Cosimi, A
在可能从异种移植物的可用性中受益的患者中，有那些肾衰竭的患者，他们对分型淋巴细胞的抗体反应性水平很高。具有高PRA（群体反应性抗体）的这些个体不太可能接受肾移植，因为他们对绝大多数潜在供体高度敏感。此外，所有人类都具有明显水平的天然抗体，对猪等远亲物种具有反应性。如果PRA和天然抗体水平之间存在相关性，那么这些患者也将面临更大的异种移植超急性排斥反应风险。因此，我们以盲法检查了PRA阳性供体血清的猪淋巴细胞反应性。将105份受试血清的亚组按PRA水平分组，并分析通过对猪淋巴细胞的补体依赖性细胞毒性试验可检测的天然抗体水平。各亚群间天然抗体滴度范围无显著性差异。因此，有没有明显的PRA水平和天然抗体水平之间的相关性，以猪lymphocyte.In此外，我们研究了11个高度致敏的患者接受肾移植和传统的三联药物免疫抑制的血清，以确定是否免疫抑制，以维持血管化的同种异体移植物对PRA和/或异种反应性的影响。平均术后PRA显著低于平均术前PRA，而异种反应性无显著差异。因此，移植前免疫抑制可以增加为高度致敏的受者鉴定相容的人类供体的机会，并且不会帮助或阻碍异种移植候选者的移植前调节。
Among the patients that might potentially benefit from the availability of xenografts are those in kidney failure who demonstrate high levels of antibody reactivity to panels of typing lymphocytes. Such individuals with high PRA (panel reactive antibody) are unlikely to receive a renal allograft because they are highly sensitized to the vast majority of potential donors. In addition, all humans have demonstrable levels of natural antibodies reactive to distantly related species such as the pig. If there were a correlation between PRA and levels of natural antibodies, then such patients would also be at greater risk for hyperacute rejection of xenografts. We have therefore examined, in a blinded fashion, the porcine lymphocyte reactivity of sera from PRA positive donors. Subsets of the 105 sera tested were grouped by PRA level and analyzed for levels of natural antibodies detectable by a complement-dependent cytotoxicity assay on porcine lymphocytes. There was no significant difference in the range of titers of natural antibodies between subsets. Thus, there was no demonstrable correlation between levels of PRA and levels of natural antibodies to porcine lymphocytes.In addition, we studied the sera of 11 highly sensitized patients who received renal allografts and conventional triple drug immunosuppression in order to determine whether immunosuppression to maintain a vascularized allograft had an effect on PRA and/or xenoreactivity. Mean post-operative PRA was significantly lower than mean pre-operative PRA, while there was no significant difference in xenoreactivity. Thus, pretransplant immunosuppression may permit an increased opportunity to identify compatible human donors for highly sensitized recipients and will not help or hinder the pre-transplant conditioning of a candidate for xenotransplantation.