C4d fixing, luminex binding antibodies - A new tool for prediction of graft failure after heart transplantation

C4d fixing, luminex binding antibodies - A new tool for prediction of graft failure after heart transplantation
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DOI:
10.1111/j.1600-6143.2007.01991.x
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发表时间:
2007-12-01
影响因子:
8.8
通讯作者:
Rose, M. L.
Rose, M. L.
中科院分区:
医学2区
文献类型:
--
作者:
Smith, J. D.;Hamour, I. M.;Rose, M. L.

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检测移植前抗体的标准方法是供者白细胞的补体依赖细胞毒性(CDC)试验。固相检测移植前血清中的HLA抗体显示致敏患者的数量较多,但其临床影响尚不确定。在这里,我们开发了一种检测Luminex珠上固定的C4D抗体的方法。对565例心脏移植患者的移植前血清进行了CDC、HLA包被Luminex小球和Luminex小球上C4D沉积的回顾性检测,结果与移植物存活率相关。565名患者中有5名在移植前有CDC阳性供者特异性抗体(DSA),而使用Luminex珠子后,这一数字增加了19人。有DSA的CDC-ve/Luminex+Ve患者(n=19)的1年生存率为42%,而无DSA的CDC-ve/Luminex+Ve患者(n=39,p=0.0039)的1年生存率为77%。C4D(22/67 Luminex阳性血清)的固定对移植物的预后有负面影响,C4D+ve/DSA+ve(n=11)20%,C4d+ve/DSA-ve(n=11)91%,C4d-ve DSA+ve(n=13)54%,C4d-ve DSA-ve(n=32)75%,抗体阴性患者为75%(p=0.0002)。总之,移植前血清Luminex+ve DSA的检测为移植物存活提供了一个强有力的阴性预测因子,尤其是当它们结合C4D时。
The standard method to detect pretransplant antibodies has been the complement dependent cytotoxicity (CDC) test of donor leukocytes. Solid phase assays to detect HLA antibodies in pretransplant serum reveal a greater number of sensitized patients, but their clinical impact is less certain. Here we have developed a method of detecting C4d fixing HLA antibodies on Luminex beads. Pretransplant serum from 565 cardiac transplant patients was retrospectively tested for the presence of HLA antibodies using CDC, HLA coated Luminex beads and C4d deposition on Luminex beads, and the results correlated with graft survival. Whereas 5/565 patients had CDC positive donor specific antibodies (DSA) before their transplant, this number was increased by 19 using Luminex beads. The 1-year survival of CDC -ve/Luminex +ve patients with DSA (n = 19) was 42% compared with 77% for CDC -ve/Luminex +ve without DSA (n = 39, p = 0.0039). Fixation of C4d (22/67 Luminex positive sera) had a negative effect on graft outcome; 1-year graft survival was, C4d +ve/DSA +ve (n = 11) 20%, C4d +ve/DSA -ve (n = 11) 91%, C4d -ve DSA +ve (n = 13) 54%, C4d -ve DSA -ve (n = 32) 75%, compared with 75% for antibody-negative patients (p = 0.0002). In conclusion, detection of Luminex +ve DSA in pretransplant serum provides a powerful negative predictor of graft survival, especially if they bind C4d.