Kimura Akio, Yoshikura Nobuaki, Koumura Akihiro, Hayashi Yuichi, Kobayashi Yuko, Kobayashi Issei, Yano Takeo, Inuzuka Takashi
Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu City, Gifu, Japan.
Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, Gifu City, Gifu, Japan.
J Proteomics. 2015 Oct 14;128:450-7. doi: 10.1016/j.jprot.2015.05.005. Epub 2015 May 12.
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.
Naturally 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.
天然存在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，脑脊液中针对神经元抗原的天然存在的自身抗体谱尚不清楚。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针对神经元抗原的天然存在的自身抗体。从77例患有各种神经系统疾病的患者中收集脑脊液样本。二维免疫印迹的抗原来源是SH-SY5Y人神经母细胞瘤细胞系。在77例患者中超过四分之一的患者（包括所有患者组）的脑脊液中发现了8个斑点，并且在静脉注射免疫球蛋白制剂中也发现了这些斑点。这些抗原斑点被鉴定为热休克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71-kDa蛋白，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；我们无法鉴定与8个斑点中的1个相对应的蛋白质名称。总之，鉴定出6种蛋白质是主要靶抗原，它们与各种神经系统疾病患者脑脊液中的天然存在的自身抗体发生反应；针对已鉴定抗原的自身抗体功能尚不清楚，可能需要进一步研究来阐明。
天然存在的自身抗体可能在组织稳态中具有重要功能。在本研究中，我们鉴定了6种常见的靶抗原，它们与患者脑脊液中的自身抗体发生反应，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，并且这些抗体的使用可能是治疗各种神经系统疾病的一种新疗法。
