A qPCR-based metric of Th2 airway inflammation in asthma.
A qPCR-based metric of Th2 airway inflammation in asthma.
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DOI：
10.1186/2045-7022-3-24
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发表时间：
2013-07-17
影响因子：
4.4
通讯作者：
Woodruff PG
中科院分区：
文献类型：
--
作者：
Bhakta NR;Solberg OD;Nguyen CP;Nguyen CN;Arron JR;Fahy JV;Woodruff PG
使用气道上皮细胞的微阵列分析，我们以前确定了一个Th 2-高分子哮喘表型的基础上，骨膜蛋白，CLCA 1和丝氨酸蛋白酶抑制剂B2的表达，其特征在于特定的炎症，重塑和治疗反应的功能。本研究的目的是开发一种基于qPCR的Th 2炎症检测方法，以克服基于微阵列方法的局限性。通过支气管镜检查从两项临床研究中获得气道上皮刷检物，该研究包括44名健康对照和62名哮喘受试者，其中39名受试者在吸入皮质类固醇（ICS）的标准化8周疗程之前和之后进行研究。将骨膜蛋白、CLCA 1和丝氨酸蛋白酶抑制剂B2的基于qPCR的表达组合成单个度量。在哮喘中，periostin、CLCA 1和serpinB 2的三个基因平均值与FeNO（r = 0.75，p = 0.0002）、血嗜酸性粒细胞（r = 0.58，p = 0.003）和PC 20乙酰甲胆碱（r =-0.65，p = 0.0006）相关，但与血清总IgE（r = 0.33，p = 0.1）无关。基线三基因平均值越高，ICS治疗第2、4和8周时FEV 1的改善越大（所有p < 0.05）。通过ROC分析，ICS治疗4周和8周时FEV 1改善的三基因平均曲线下面积（AUC）分别为0.94和0.87，高于FeNO、血嗜酸性粒细胞、IgE或PC 20的AUC。通过这三个基因平均值测量的Th 2气道炎症也具有改善症状的预测能力。在气道上皮刷拭中，periostin、CLCA 1和serpinB 2的三个基因平均值识别Th 2高和低群体，与其他Th 2生物标志物相关，并且对于ICS改善FEV 1的预测表现良好。三基因平均值提供了临床相关的Th 2气道炎症的测量，并且可以用作评估非侵入性生物标志物以预测对现有和新兴哮喘疗法的治疗反应的有价值的工具。
Using microarray profiling of airway epithelial cells, we previously identified a Th2-high molecular phenotype of asthma based on expression of periostin, CLCA1 and serpinB2 and characterized by specific inflammatory, remodeling, and treatment response features. The goal of the current study was to develop a qPCR-based assay of Th2 inflammation to overcome the limitations of microarray-based methods. Airway epithelial brushings were obtained by bronchoscopy from two clinical studies comprising 44 healthy controls and 62 subjects with asthma, 39 of whom were studied before and after a standardized 8 week course of inhaled corticosteroids (ICS). The qPCR-based expression of periostin, CLCA1 and serpinB2 were combined into a single metric. In asthma, the three-gene-mean of periostin, CLCA1 and serpinB2 correlated with FeNO (r = 0.75, p = 0.0002), blood eosinophils (r = 0.58, p = 0.003) and PC20 methacholine (r = -0.65, p = 0.0006), but not total serum IgE (r = 0.33, p = 0.1). Higher baseline three-gene-mean correlated with greater improvement in FEV1 with ICS at 2, 4 and 8 weeks (all p < 0.05). By ROC analysis, the area under the curve (AUC) of the three-gene-mean for FEV1 improvement with ICS at 4 and 8 weeks was 0.94 and 0.87, respectively, which are higher than the AUCs of FeNO, blood eosinophils, IgE or PC20. Th2 airway inflammation as measured by this three-gene-mean also had predictive capacity for an improvement in symptoms. The three-gene-mean of periostin, CLCA1 and serpinB2 in airway epithelial brushings identifies Th2-high and low populations, is correlated with other Th2 biomarkers, and performs well for prediction of FEV1 improvement with ICS. The three-gene-mean provides a measurement of Th2 airway inflammation that is clinically relevant and that can serve as a valuable tool to evaluate non-invasive biomarkers to predict treatment responses to existing and emerging asthma therapies.