Measures of gene expression in sputum cells can identify T_H2-high and T_H2-low subtypes of asthma

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• 作者：Michael C. Peters ; Zesemayat K. Mekonnen ; Shaopeng Yuan ; Nirav R. Bhakta ; Prescott G. Woodruff ; John V. Fahy
• 关键词：Asthma ; phenotypes ; TH2 cell ; mast cells ; eotaxin ; inflammation ; sputum ; cytokines ; eosinophils ; IL-4 ; IL-5 ; IL-13 ; IL-17
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：February, 2014
• 年：2014
• 卷：133
• 期：2
• 页码：388-394.e5
• 全文大小：819 K

文摘

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Background

The 3-gene signature of periostin, chloride channel accessory 1 (CLCA1), and Serpin 尾2 (SERPINB2) in airway epithelial brushings is used to classify asthma into T_H2-high and T_H2-low endotypes. Little is known about the utility of gene profiling in sputum as a molecular phenotyping method.

Objective

We sought to determine whether gene profiling in sputum cells can identify T_H2-high and T_H2-low subtypes of asthma.

Methods

In induced sputum cell pellets from 37 asthmatic patients and 15 healthy control subjects, PCR was used to profile gene expression of the epithelial cell signature of IL-13 activation (periostin, CLCA1, and SERPINB2), T_H2 genes (IL4,聽IL5, and IL13), and other genes associated with airway T_H2 inflammation.

Results

Gene expression levels of CLCA1 and periostin, but not SerpinB2, were significantly higher than normal in sputum cells from asthmatic subjects. Expression levels of IL-4, IL-5, and IL-13 were also significantly increased in asthmatic patients and highly correlated within individual subjects. By combining the expression levels of IL-4, IL-5, and IL-13 in a single quantitative metric (鈥淭_H2 gene mean鈥?, 26 (70%) of the 37 asthmatic patients had T_H2-high asthma, which was characterized by more severe measures of asthma and increased blood and sputum eosinophilia. T_H2 gene mean values tended to be stable when initial values were very high or very low but fluctuated above or below the T_H2-high cutoff when initial values were intermediate.

Conclusion

IL-4, IL-5, and IL-13 transcripts are easily detected in sputum cells from asthmatic patients, and their expression levels can be used to classify asthma into T_H2-high and T_H2-low endotypes.