Nieto-Fontarigo Juan José, González-Barcala Francisco Javier, Andrade-Bulos Luis Juan, San-José María Esther, Cruz María Jesús, Valdés-Cuadrado Luis, Crujeiras Rosa María, Arias Pilar, Salgado Francisco Javier
Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Department of Medicine, Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Allergy. 2020 Dec;75(12):3171-3183. doi: 10.1111/all.14406. Epub 2020 Jul 3.
Asthma is heterogeneous disease with different phenotypes, endotypes and severities. Definition of these subgroups requires the identification of biomarkers in biological samples, and serum proteomics is a useful and minimally invasive method for this purpose. Therefore, the aim of this study was to detect serum proteins whose abundance is distinctively associated with different asthma phenotypes (allergic vs nonallergic) or severities.
For each group of donors (32 healthy controls, 43 allergic rhinitis patients and 192 asthmatics with different phenotypes and severities), we generated two pools of sera that were analysed by a shotgun MS approach based on combinatorial peptide ligand libraries and iTRAQ-LC-MS/MS.
MS analyses identified 18 proteins with a differential abundance. Functional/network study of these proteins identified key processes for asthma pathogenesis, such as complement activation, extracellular matrix organization, platelet activation and degranulation, or post-translational protein phosphorylation. Furthermore, our results highlighted an enrichment of the "Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)" route in allergic asthma and the lectin pathway of complement activation in nonallergic asthma. Thus, several proteins (eg IGFALS, HSPG2, FCN2 or MASP1) displayed a differential abundance between the different groups of donors. Particularly, our results revealed IGFALS as a useful biomarker for moderate-severe allergic asthma.
Our data suggest a set of serum biomarkers, especially IGFALS, capable of differentiating allergic from nonallergic asthma. These proteins reveal different pathophysiological mechanisms and may be useful in the future for diagnosis, prognosis or targeted therapy purposes.
哮喘是一种具有不同表型、内型和严重程度的异质性疾病。定义这些亚组需要在生物样本中鉴定生物标志物，而血清蛋白质组学是实现这一目的的一种有用且微创的方法。因此，本研究的目的是检测其丰度与不同哮喘表型（过敏性与非过敏性）或严重程度有显著关联的血清蛋白。
对于每组供体（32名健康对照者、43名过敏性鼻炎患者和192名具有不同表型和严重程度的哮喘患者），我们制备了两池血清，通过基于组合肽配体库和iTRAQ-LC-MS/MS的鸟枪法质谱方法进行分析。
质谱分析鉴定出18种丰度有差异的蛋白质。对这些蛋白质的功能/网络研究确定了哮喘发病机制的关键过程，如补体激活、细胞外基质组织、血小板激活和脱颗粒，或蛋白质翻译后磷酸化。此外，我们的结果突出了过敏性哮喘中“胰岛素样生长因子结合蛋白（IGFBPs）对胰岛素样生长因子（IGF）转运和摄取的调节”途径以及非过敏性哮喘中补体激活的凝集素途径的富集。因此，几种蛋白质（如IGFALS、HSPG2、FCN2或MASP1）在不同供体组之间表现出丰度差异。特别是，我们的结果表明IGFALS是中重度过敏性哮喘的一种有用生物标志物。
我们的数据表明一组血清生物标志物，尤其是IGFALS，能够区分过敏性哮喘和非过敏性哮喘。这些蛋白质揭示了不同的病理生理机制，未来可能在诊断、预后或靶向治疗中发挥作用。
