A novel strategy to identify autoantigens by proteomic analysis of plasma IgG-bound proteins

Takuya Toki, Y. Kodera, Ryo Konno, Yoshiya Hirata, Tatsuya Saito, M. Shichiri
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引用次数: 1

Abstract

Autoimmune mechanisms have been hypothesized to underlie a number of human disorders in which both disease pathogenesis and diagnostic biomarkers remain poorly understood. This is partly due to a lack of efficient techniques for identification of plasma autoantibodies associated with specific pathophysiological conditions. We have developed a novel proteomic methodology to comprehensively identify plasma IgG-bound proteins using liquid chromatography tandem mass spectrometry (LC-MS/MS) after denaturing enriched plasma IgG to solubilize and release low molecular weight proteins. In total, we identified 44 proteins using this method that were undetectable in unprocessed plasma, 21 of which were not identified in the Human Plasma Proteome Draft of 2017. Comparison of plasma IgGbound proteins between healthy subjects and patients with isolated adrenocorticotropic hormone deficiency, a rare endocrine disorder speculated to involve autoimmune mechanisms, revealed several distinct IgG-bound proteins specifically detected in patient plasma but not in healthy subjects. Our results suggest that solubilization of low molecular weight proteins bound to enriched plasma IgG and subsequent proteomic analysis by LC-MS/MS could provide a promising strategy for identification of autoantigens in human peripheral blood.
通过血浆igg结合蛋白的蛋白质组学分析鉴定自身抗原的新策略
自身免疫机制被假设为许多人类疾病的基础,其中疾病发病机制和诊断生物标志物仍然知之甚少。这部分是由于缺乏有效的技术来鉴定与特定病理生理条件相关的血浆自身抗体。我们开发了一种新的蛋白质组学方法,利用液相色谱串联质谱(LC-MS/MS)对富集的血浆IgG进行变性后溶解并释放低分子量蛋白质,从而全面鉴定血浆IgG结合蛋白。总体而言,我们使用该方法鉴定了44种在未经处理的血浆中无法检测到的蛋白质,其中21种在2017年人类血浆蛋白质组草案中未被鉴定。比较健康人与孤立性促肾上腺皮质激素缺乏症(一种推测与自身免疫机制有关的罕见内分泌疾病)患者的血浆igg结合蛋白,发现在患者血浆中特异性检测到几种不同的igg结合蛋白,但在健康人血浆中未检测到。我们的研究结果表明,将低分子量蛋白与富集的血浆IgG结合,然后通过LC-MS/MS进行蛋白质组学分析,可以为鉴定人外周血中的自身抗原提供一种有前途的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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