Discriminatory Molecular Biomarkers of Allergic and Nonallergic Asthma and Its Severity
Discriminatory Molecular Biomarkers of Allergic and Nonallergic Asthma and Its Severity
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DOI：
10.3389/fimmu.2019.01051
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发表时间：
2019-05-09
影响因子：
7.3
通讯作者：
Cardaba, Blanca
中科院分区：
文献类型：
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作者：
Baos, Selene;Calzada, David;Cardaba, Blanca
哮喘是一种复杂的疾病，包含各种表型和内型，所有这些仍然需要可靠的生物标志物进行准确分类。在之前的一项研究中，我们通过研究由 4 组受试者组成的人群中 94 个基因的表达来定义与哮喘和呼吸道过敏相关的特定基因：健康对照、非过敏性哮喘、哮喘过敏和非哮喘过敏患者。对对照组和患者之间差异基因表达的分析揭示了一组主要与疾病严重程度相关的统计相关基因，即 CHI3L1、IL-8、IL-10、MSR1、PHLDA1、PI3 和 SERPINB2。在这里，我们分析了这些基因及其蛋白质是否可能是潜在的哮喘生物标志物，以区分非过敏性哮喘和哮喘过敏受试者。通过 ELISA（血清）或蛋白质印迹（从外周血单核细胞或 PBMC 提取的蛋白质）测定蛋白质定量。使用 Graph-Pad 程序通过非配对 t 检验进行统计分析。使用 R 程序通过受试者工作特征 (ROC) 曲线分析来确定区分两组（以及严重程度亚组）的几种候选生物标志物的基因和蛋白质表达的敏感性和特异性。 ROC曲线分析确定单基因对于区分一些表型具有良好的敏感性和特异性。然而，使用可重复的技术在易于获得的样品中发现了两种或三种蛋白质生物标志物的有趣组合，可以区分哮喘疾病和该病理学不同表型之间的疾病严重程度。由单一生物标志物和生物标志物组合形成的基因和蛋白质组已在易于获得的样品中并通过标准化技术进行了定义。这些面板可用于表征哮喘表型，特别是在区分哮喘严重程度时。
Asthma is a complex disease comprising various phenotypes and endotypes, all of which still need solid biomarkers for accurate classification. In a previous study, we defined specific genes related to asthma and respiratory allergy by studying the expression of 94 genes in a population composed of 4 groups of subjects: healthy control, nonallergic asthmatic, asthmatic allergic, and nonasthmatic allergic patients. An analysis of differential gene expression between controls and patients revealed a set of statistically relevant genes mainly associated with disease severity, i.e., CHI3L1, IL-8, IL-10, MSR1, PHLDA1, PI3, and SERPINB2. Here, we analyzed whether these genes and their proteins could be potential asthma biomarkers to distinguish between nonallergic asthmatic and asthmatic allergic subjects. Protein quantification was determined by ELISA (in serum) or Western blot (in protein extracted from peripheral blood mononuclear cells or PBMCs). Statistical analyses were performed by unpaired t-test using the Graph-Pad program. The sensitivity and specificity of the gene and protein expression of several candidate biomarkers in differentiating the two groups (and the severity subgroups) was performed by receiver operating characteristic (ROC) curve analysis using the R program. The ROC curve analysis determined single genes with good sensitivity and specificity for discriminating some of the phenotypes. However, interesting combinations of two or three protein biomarkers were found to distinguish the asthma disease and disease severity between the different phenotypes of this pathology using reproducible techniques in easy-to-obtain samples. Gene and protein panels formed by single biomarkers and biomarker combinations have been defined in easily obtainable samples and by standardized techniques. These panels could be useful for characterizing phenotypes of asthma, specifically when differentiating asthma severity.