Measures of gene expression in sputum cells can identify T H2-high and TH2-low subtypes of asthma

Abstract

Background The 3-gene signature of periostin, chloride channel accessory 1 (CLCA1), and Serpin β2 (SERPINB2) in airway epithelial brushings is used to classify asthma into TH2-high and TH2-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 TH2-high and TH2-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), TH2 genes (IL4, IL5, and IL13), and other genes associated with airway TH2 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 ("TH2 gene mean"), 26 (70%) of the 37 asthmatic patients had TH2-high asthma, which was characterized by more severe measures of asthma and increased blood and sputum eosinophilia. TH2 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 TH2-high and TH2-low endotypes. © 2013 American Academy of Allergy, Asthma & Immunology.