Proteomic profiling of antigens in circulating immune complexes associated with each of seven autoimmune diseases

Proteomic profiling of antigens in circulating immune complexes associated with each of seven autoimmune diseases
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DOI:
10.1016/j.clinbiochem.2014.11.008
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发表时间:
2015-02-01
影响因子:
2.8
通讯作者:
Kuroda, Naotaka
Kuroda, Naotaka
中科院分区:
医学3区
文献类型:
--
作者:
Ohyama, Kaname;Baba, Miyako;Kuroda, Naotaka

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目的:免疫复合物(IC)触发体液免疫反应。因此,IC内成分抗原的鉴定与游离抗原的鉴定具有截然不同的临床意义。 设计和方法:在这里,我们将血清的免疫复合体分析应用于七种主要自身免疫性疾病的研究——抗中性粒细胞胞浆抗体相关性血管炎、大动脉炎、混合结缔组织病、皮肌炎、干燥综合征、系统性硬皮病和系统性红斑狼疮——以及健康供体全面鉴定纳入循环 IC 的抗原并寻找疾病特异性抗原。结果:我们使用此方法鉴定了 468 种不同的 IC 相关抗原。重要的是,其中 62 个抗原是疾病特异性抗原,并且七种自身免疫性疾病中的每一种都至少有 3 个疾病特异性抗原。在已鉴定的疾病特异性抗原中,含有卷曲螺旋结构域的蛋白 158 和血影蛋白被鉴定为分别对 SSc 和 SS 发病机制重要的潜在自身抗原;据报道,在 SSc 和 SS 患者中分别发现了显着的肌联蛋白和血影蛋白自身抗体。结论:免疫复合体分析可能普遍适用于动物和人类中 IC 与自身免疫性疾病之间关系的研究。 (C) 2014 年加拿大临床化学家协会。由爱思唯尔公司出版。保留所有权利。
Objective: Immune complexes (ICs) trigger humoral immune responses. Therefore, the identification of constituent antigens within ICs would have very different clinical significance than identification of free antigens.Design and methods: Here, we applied immune complexome analysis of serum to the study of seven major autoimmune diseases-anti-neutrophil cytoplasmic antibody-associated vasculitis, Takayasu's arteritis, mixed connective tissue disease, dermatomyositis, Sjogren's syndrome, systemic scleroderma, and systemic lupus erythematosus-and healthy donors to comprehensively identify antigens incorporated into circulating ICs and to find disease-specific antigens.Results: We identified 468 distinct IC-associated antigens using this method. Importantly, 62 of those antigens were disease-specific antigens, and there were at least three disease-specific antigens for each of the seven autoimmune diseases. Of the disease-specific antigens identified, coiled-coil domain-containing protein 158 and spectrin were identified as potential autoantigens important to SSc and SS pathogenesis, respectively; notable titin and spectrin autoantibodies are reportedly found in SSc and SS patients, respectively.Conclusion: Immune complexome analysis may be generally applicable to the study of the relationship between ICs and autoimmune diseases in animals and humans. (C) 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.