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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients.
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Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients.

机译：对外周血单核细胞表达的基因进行分析可预测哮喘患者的糖皮质激素敏感性。

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摘要

Gene expression profiles were examined in freshly isolated peripheral blood mononuclear cells (PBMC) from two independent cohorts (training and test sets) of glucocorticoid (GC)-sensitive (n = 64) and GC-resistant (n = 42) asthma patients in search of genes that accurately predict responders and nonresponders to inhaled corticosteroids. A total of 11,812 genes were examined with high-density oligonucleotide microarrays in both resting PBMC (106 patients) and cells treated in vitro with IL-1beta and TNF-alpha combined (88 patients), with or without GC. A total of 5,011 genes were expressed at significant levels in the PBMC, and 1,334 of those were notably up-regulated or down-regulated by IL-1beta/TNF-alpha treatment. The expression changes of 923 genes were significantly reversed in GC responders in the presence of GC. The expression pattern of 15 of these 923 genes that most accurately separated GC responders (n = 26) from the nonresponders (n = 18) in the training set, based on the weighted voting algorithm, predicted the independent test set of equal size with 84% accuracy. The expression accuracy of these genes was confirmed by real-time-quantitative PCR, wherein 11 of the 15 genes predicted GC sensitivity at baseline with 84% accuracy, with one gene predicting at 81% in an independent cohort of 79 patients. We conclude that we have uncovered gene expression profiles in PBMC that predict clinical response to inhaled GC therapy with meaningful accuracy. Upon validation in an independent study, these results support the development of a diagnostic test to guide GC therapy in asthma patients.
机译：在两个独立的糖皮质激素敏感型（n = 64）和抗药性耐药（n = 42）哮喘患者的独立队列（训练和测试集）中检查了新鲜分离的外周血单个核细胞（PBMC）中的基因表达谱准确预测吸入皮质类固醇的反应者和非反应者的基因在静息PBMC（106例患者）和用IL-1beta和TNF-α联合体外治疗的细胞（88例）中，无论有无GC，都用高密度寡核苷酸微阵列检查了总共11,812个基因。 PBMC中共有5,011个基因以显着水平表达，其中1,334个基因通过IL-1beta / TNF-alpha处理显着上调或下调。在存在GC的情况下，GC响应者中923个基因的表达变化明显逆转。基于加权投票算法，这923个基因中的15个的表达模式能够最准确地将训练组中的GC响应者（n = 26）与非响应者（n = 18）分开，从而预测了大小相等的独立测试集（84个） ％ 准确性。这些基因的表达准确性已通过实时定量PCR证实，其中15个基因中有11个在基线时预测GC敏感性为84％准确度，而在79个患者的独立队列中，一个基因预测为81％。我们得出的结论是，我们已经在PBMC中发现了基因表达谱，该基因谱以有意义的准确性预测了对吸入式GC治疗的临床反应。经过一项独立研究的验证，这些结果支持了开发诊断性试验以指导哮喘患者进行GC治疗。

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