Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma.
Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma.
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DOI：
10.3389/fmed.2020.561866
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发表时间：
2020
影响因子：
3.9
通讯作者：
Hamoudi R
中科院分区：
文献类型：
--
作者：
Hachim MY;Elemam NM;Ramakrishnan RK;Salameh L;Olivenstein R;Hachim IY;Venkatachalam T;Mahboub B;Al Heialy S;Halwani R;Hamid Q;Hamoudi R
背景：双调蛋白（AREG）在哮喘气道和痰中的表达增加，并与哮喘相关。然而，没有研究进行评估哮喘患者的血液和唾液中的AREG水平。目的：检测支气管哮喘患者血液、唾液和支气管活检标本中循环AREG mRNA和蛋白的浓度。研究方法：与健康对照相比，使用ELISA测量非重度和重度哮喘患者的血浆和唾液AREG蛋白浓度，同时通过RT qPCR测量PBMCs和唾液mRNA表达。评估原代哮喘支气管上皮细胞和成纤维细胞的AREG mRNA表达，并在其条件培养基中释放可溶性AREG。AREG的组织表达采用哮喘患者和健康对照的支气管活检的免疫组化进行评估。探索了公开可用的转录组数据库中支气管上皮的总体转录组谱，并探索了哮喘与健康对照中PBMC的AREG表达。结果：哮喘患者血液和唾液中AREG蛋白水平高于对照组。在唾液和原代支气管上皮细胞中也观察到较高的mRNA表达，以及支气管活检中较高的AREG免疫反应性。血液和唾液AREG水平与过敏性鼻炎状态、特应性状态、湿疹状态、血浆骨膜蛋白、嗜酸性粒细胞、孟鲁司特钠使用、ACT评分、FEV 1和FEV 1/FVC呈正相关。计算机模拟分析显示，AREG基因高表达的严重哮喘支气管上皮细胞与较高的中性粒细胞浸润相关。结论：在非过敏性重度哮喘中，微创血液样本和非侵入性唾液样本中测量的AREG水平较高。这是第一份报告显示非过敏性严重哮喘患者血液和唾液中AREG水平较高。
Background: Amphiregulin (AREG) expression in asthmatic airways and sputum was shown to increase and correlate with asthma. However, no studies were carried out to evaluate the AREG level in blood and saliva of asthmatic patients. Objective: To measure circulating AREG mRNA and protein concentrations in blood, saliva, and bronchial biopsies samples from asthmatic patients. Methods: Plasma and Saliva AREG protein concentrations were measured using ELISA while PBMCs, and Saliva mRNA expression was measured by RT qPCR in non-severe, and severe asthmatic patients compared to healthy controls. Primary asthmatic bronchial epithelial cells and fibroblasts were assessed for AREG mRNA expression and released soluble AREG in their conditioned media. Tissue expression of AREG was evaluated using immunohistochemistry of bronchial biopsies from asthmatic patients and healthy controls. Publicly available transcriptomic databases were explored for the global transcriptomic profile of bronchial epithelium, and PBMCs were explored for AREG expression in asthmatic vs. healthy controls. Results: Asthmatic patients had higher AREG protein levels in blood and saliva compared to control subjects. Higher mRNA expression in saliva and primary bronchial epithelial cells plus higher AREG immunoreactivity in bronchial biopsies were also observed. Both blood and saliva AREG levels showed positive correlations with allergic rhinitis status, atopy status, eczema status, plasma periostin, neutrophilia, Montelukast sodium use, ACT score, FEV1, and FEV1/FVC. In silico analysis showed that severe asthmatic bronchial epithelium with high AREG gene expression is associated with higher neutrophils infiltration. Conclusion: AREG levels measured in a minimally invasive blood sample and a non-invasive saliva sample are higher in non-allergic severe asthma. This is the first report to show the higher level of AREG levels in blood and saliva of non-allergic severe asthma.
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影响因子：
8.7
作者：
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通讯作者：
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影响因子：
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DOI：
10.1152/ajplung.00390.2014
发表时间：
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