Identification of endothelial cell surface antigens encoded by genes other than HLA. A combined immunoprecipitation and proteomic approach for the identification of antigens recognized by antibodies against endothelial cells in transplant recipients
Identification of endothelial cell surface antigens encoded by genes other than HLA. A combined immunoprecipitation and proteomic approach for the identification of antigens recognized by antibodies against endothelial cells in transplant recipients
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DOI：
10.1016/j.humimm.2013.05.002
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发表时间：
2013-11-01
期刊：
影响因子：
2.7
通讯作者：
Stastny, Peter
中科院分区：
文献类型：
--
作者：
Qin, Zhiqiang;Zou, Yizhou;Stastny, Peter
一段时间以来，人们已经知道移植受体可能具有在淋巴细胞上检测不到的内皮细胞抗体。然而，在这些内皮抗原的分析方面几乎没有取得进展。在本实验中，我们试图表征内皮细胞表面抗原，在移植排斥反应过程中产生抗体。我们使用了一组来自脐带静脉的内皮细胞，发现该组中具有多态性模式的抗体似乎与同种异体肾移植失败和心脏移植受者中移植相关冠状动脉疾病（TCAD）的发展相关。在39名肾同种异体移植患者中，21名内皮细胞抗体呈阴性且表现良好，18名内皮细胞抗体呈阳性且经常出现移植失败（p = 0.001）。在18例TCAD患者和20例无TCAD的对照组患者中，观察到冠状动脉疾病与内皮细胞抗体的相关性（p < 0.02）。为了表征负责这些血清学反应的内皮抗原，我们用相应的内皮细胞表面抗原对反应性抗体进行免疫沉淀，然后对靶抗原进行蛋白质鉴定。在这些实验中鉴定了9种蛋白质，5种是非多态性的，似乎代表自身抗原。四个分离的蛋白质似乎是多态性的。它们是人类主要组织相容性复合物I类链相关基因A（云母），已知与抗体产生和移植失败相关，人角蛋白1，已知是多态性的，并在内皮细胞表面表达的蛋白质，真核翻译起始因子（EIF）2A和ErbB3结合蛋白1。角蛋白1和其他抗原在同种异体移植排斥反应中的可能作用需要进一步研究。(C)2013年由Elsevier Inc.出版美国组织相容性和免疫遗传学学会（American Society for Histocompatibility and Immunogenetics）
It has been known for some time that transplant recipients may have antibodies to endothelial cells which are not detected on lymphocytes. However, little progress has been made in the analysis of these endothelial antigens. In the present experiments we have attempted to characterize endothelial cell surface antigens to which antibodies were produced during graft rejection. We have used a panel of endothelial cells from umbilical cord veins and found that antibodies with a polymorphic pattern in the panel appeared to correlate with transplant failure of kidney allografts and with the development of transplant-related coronary artery disease (TCAD) in heart transplant recipients. Among 39 patients with kidney allografts, 21 were negative for antibodies to endothelial cells and did well and 18 were positive and had frequent transplant loss (p = 0.001). In 18 patients with TCAD and 20 patients of a comparator group without TCAD, association of coronary disease with endothelial cell antibodies was observed (p < 0.02). To characterize the endothelial antigens responsible for these serologic reactions we performed immuno-precipitation of reactive antibodies with the corresponding endothelial cell surface antigens, followed by protein identification of the target antigens. Nine proteins were identified in these experiments, 5 were non-polymorphic and appeared to represent autoantigens. Four of the isolated proteins appeared to be polymorphic. They were the Human Major Histocompatibility Complex class I chain-related gene A (MICA), already known to be associated with antibody production and graft failure, human keratin 1, a protein known to be polymorphic and expressed on the surface of endothelial cells, eukaryotic translation initiation factor (EIF) 2A and ErbB3-binding protein 1. The possible role of keratin 1 and the other antigens in allograft rejection requires further investigation. (C) 2013 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.