The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden.
Allergy. 2011 Jan;66(1):132-40. doi: 10.1111/j.1398-9995.2010.02444.x.
Glucocorticoids (GCs) may affect the expression of hundreds of genes in different cells and tissues from patients with intermittent allergic rhinitis (IAR). It is a formidable challenge to understand these complex changes by studying individual genes. In this study, we aimed to identify (i) pathways affected by local GC treatment and (ii) examine if those pathways could be used to find novel markers of local GC treatment in nasal fluids from patients with IAR.
Gene expression microarray- and iTRAQ-based proteomic analyses of nasal fluids, nasal fluid cells and nasal mucosa from patients with IAR were performed to find pathways enriched for differentially expressed genes and proteins. Proteins representing those pathways were analyzed with ELISA in an independent material of nasal fluids from 23 patients with IAR before and after treatment with a local GC.
Transcriptomal and proteomic high-throughput analyses of nasal fluids, nasal fluid cells and nasal mucosal showed that local GC treatment affected a wide variety of pathways in IAR such as the glucocorticoid receptor pathway and the acute phase response pathway. Extracellular proteins encoded by genes in those pathways were analyzed in an independent material of nasal fluids from patients. Proteins that changed significantly in expression included known biomarkers such as eosinophil cationic protein but also proteins that had not been previously described in IAR, namely CCL2, M-CSF, CXCL6 and apoH.
Pathway-based analyses of genomic and proteomic high-throughput data can be used as a complementary approach to identify novel potential markers of GC treatment in IAR.
糖皮质激素（GCs）可能会影响间歇性过敏性鼻炎（IAR）患者不同细胞和组织中数百个基因的表达。通过研究单个基因来理解这些复杂的变化是一项艰巨的挑战。在这项研究中，我们旨在确定：（i）受局部 GC 治疗影响的途径；（ii）检查这些途径是否可用于在 IAR 患者的鼻液中找到局部 GC 治疗的新标志物。
对 IAR 患者的鼻液、鼻液细胞和鼻黏膜进行基因表达微阵列和 iTRAQ 基于蛋白质组学分析，以找到差异表达基因和蛋白质富集的途径。使用 ELISA 分析这些途径的蛋白质在 23 例 IAR 患者的鼻液中进行独立治疗前后的分析。
鼻液、鼻液细胞和鼻黏膜的转录组学和蛋白质组学高通量分析表明，局部 GC 治疗会影响 IAR 中的多种途径，如糖皮质激素受体途径和急性期反应途径。对这些途径中的基因编码的细胞外蛋白进行了分析，发现了在患者鼻液中的独立样本中表达发生显著变化的蛋白，包括已知的生物标志物，如嗜酸性粒细胞阳离子蛋白，但也包括以前在 IAR 中未描述过的蛋白，即 CCL2、M-CSF、CXCL6 和 apoH。
基于途径的基因组和蛋白质组学高通量数据分析可作为一种补充方法，用于鉴定 IAR 中 GC 治疗的新潜在标志物。
