Identification of target antigens of naturally occurring autoantibodies in
Identification of target antigens of naturally occurring autoantibodies in
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天然存在的自身抗体的靶抗原的鉴定
DOI：
10.1016/j.jprot.2015.05.005
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发表时间：
2015
期刊：
影响因子：
3.3
通讯作者：
Inuzuka T.
中科院分区：
文献类型：
--
作者：
Kimura A;Yoshikura N;Koumura A;Hayashi Y;Kobayashi I;Yano T;Inuzuka T.
自然产生的自身抗体具有与正常细胞过程相关的自然生理功能。然而，脑脊液中天然存在的针对神经元抗原的自身抗体的种类尚不清楚。本研究的目的是通过基于蛋白质组学的分析，鉴定各种神经系统疾病患者脑脊液中天然存在的针对神经元抗原的自身抗体。脑脊液样本采集自77例不同神经系统疾病患者。二维免疫印迹的抗原来源为SH-SY5Y人神经母细胞瘤细胞系。77例患者（包括所有患者组）中有超过四分之一的患者在脑脊液中识别出8个斑点，这些斑点在静脉免疫球蛋白制剂中被识别。这些抗原斑点分别为热休克105-kDa/110-kDa蛋白1、异构体CRA_b、78-kDa葡萄糖调节蛋白、热休克同源蛋白71-kDa、微管蛋白β链、波形蛋白（2个斑点）和60-kDa热休克蛋白、线粒体；我们无法识别8个位点中1个对应的蛋白质名称。综上所述，有6种蛋白被鉴定为主要靶抗原，可与各种神经系统疾病患者脑脊液中天然存在的自身抗体发生反应；自身抗体对所鉴定抗原的作用尚不清楚，可能需要进一步的研究来澄清。自然产生的自身抗体可能在组织稳态中起重要作用。在这项研究中，我们发现了6种与患者脑脊液（CSF）自身抗体反应的常见靶抗原，与疾病类型无关。这些发现可能阐明脑脊液中天然存在的自身抗体的重要性，这些抗体的使用可能是治疗各种神经系统疾病的一种新方法。
Naturally occurring autoantibodies have natural physiologic functions related to normal cell processes. However, the repertoire of naturally occurring autoantibodies against neuronal antigens in CSF is unclear. The purpose of this study was to identify naturally occurring autoantibodies against neuronal antigens in CSF from patients with various neurologic diseases by proteomics-based analysis. The CSF samples were collected from 77 patients with various neurologic disorders. The antigen source for 2-dimensional immunoblotting was the SH-SY5Y human neuroblastoma cell line. There were 8 spots recognized in CSF from more than one-fourth of the 77 patients including all patient groups and these spots were recognized in intravenous immunoglobulin preparations. These antigen spots were identified as heat shock 105-kDa/110-kDa protein 1, isoform CRA_b, 78-kDa glucose-regulated protein, heat shock cognate 71-kDa protein, tubulin beta chain, vimentin (2 spots), and 60-kDa heat shock protein, mitochondrial; we could not identify the protein name corresponding to 1 of the 8 spots. In summary, there were 6 proteins identified that were main target antigens that reacted with naturally occurring autoantibodies in CSF from patients with varied neurologic disorders; the functions of autoantibodies against the identified antigens are unknown and may be clarified with further studies.Biological significanceNaturally occurring autoantibodies may have important functions in tissue homeostasis. In this study, we identified 6 common target antigens that reacted with autoantibodies in cerebrospinal fluid (CSF) from patients, independent of disease type. These findings may clarify the importance of naturally occurring autoantibodies in CSF and the use of these antibodies potentially may be a novel therapy for various neurologic disorders.