Immunology Department, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
J Biol Regul Homeost Agents. 2013 Apr-Jun;27(2):337-50.
Analysis of gene-expression profiles by microarrays is useful for characterization of candidate genes, key regulatory networks, and to define phenotypes or molecular signatures which improve the diagnosis and/or classification of the allergic processes. We have used this approach in the study of olive pollen response in order to find differential molecular markers among responders and non-responders to this allergenic source. Five clinical groups, non-allergic, asymptomatic, allergic but not to olive pollen, untreated-olive-pollen allergic patients and olive-pollen allergic patients (under specific-immunotherapy), were assessed during and outside pollen seasons. Whole-genome gene expression analysis was performed in RNAs extracted from PBMCs. After assessment of data quality and principal components analysis (PCA), differential gene-expression, by multiple testing and, functional analyses by KEGG, for pathways and Gene-Ontology for biological processes were performed. Relevance was defined by fold change and corrected P values (less than 0.05). The most differential genes were validated by qRT-PCR in a larger set of individuals. Interestingly, gene-expression profiling obtained by PCA clearly showed five clusters of samples that correlated with the five clinical groups. Furthermore, differential gene expression and functional analyses revealed differential genes and pathways in the five clinical groups. The 93 most significant genes found were validated, and one set of 35 genes was able to discriminate profiles of olive pollen response. Our results, in addition to providing new information on allergic response, define a possible molecular signature for olive pollen allergy which could be useful for the diagnosis and treatment of this and other sensitizations.
通过微阵列进行基因表达谱分析有助于鉴定候选基因、关键调控网络,并定义改善过敏过程的诊断和/或分类的表型或分子特征。我们已经在研究橄榄花粉反应中使用了这种方法,以寻找对这种过敏原有反应和无反应的个体之间的差异分子标记。在花粉季节和花粉季节之外,评估了五个临床组,即非过敏、无症状、对橄榄花粉过敏但不过敏、未经治疗的橄榄花粉过敏患者和橄榄花粉过敏患者(在特定免疫治疗下)。从 PBMCs 中提取的 RNA 进行全基因组基因表达分析。在评估数据质量和主成分分析 (PCA) 后,通过多重测试和功能分析(KEGG 途径和基因本体论的生物过程)进行差异基因表达。相关性由倍数变化和校正的 P 值(小于 0.05)定义。通过 qRT-PCR 在更大的个体样本中验证了最差异的基因。有趣的是,通过 PCA 获得的基因表达谱清楚地显示了与五个临床组相关的五个样本簇。此外,差异基因表达和功能分析揭示了五个临床组中的差异基因和途径。发现了 93 个最显著的基因进行了验证,其中一组 35 个基因能够区分橄榄花粉反应的谱。除了提供过敏反应的新信息外,我们的结果还定义了橄榄花粉过敏的可能分子特征,这可能对这种和其他致敏的诊断和治疗有用。