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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:133

Article

Peters, Michael C.^1,2  Mekonnen, Zesemayat K.²  Yuan, Shaopeng²  Bhakta, Nirav R.^1,2  Woodruff, Prescott G.^1,2  Fahy, John V.^1,2 

[1] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA

关键词: Asthma;    phenotypes;    T(H)2 cell;    mast cells;    eotaxin;    inflammation;    sputum;    cytokines;    eosinophils;    IL-4;    IL-5;    IL-13;    IL-17;   

DOI  :  10.1016/j.jaci.2013.07.036

来源: Elsevier

【 摘 要 】

Background: The 3-gene signature of periostin, chloride channel accessory 1 (CLCA1), and Serpin beta 2 (SERPINB2) in airway epithelial brushings is used to classify asthma into T(H)2-high and T(H)2-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(H)2-high and T(H)2-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(H)2 genes (IL4, IL5, and IL13), and other genes associated with airway T(H)2 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 (T(H)2 gene mean), 26 (70%) of the 37 asthmatic patients had T(H)2-high asthma, which was characterized by more severe measures of asthma and increased blood and sputum eosinophilia. T(H)2 gene mean values tended to be stable when initial values were very high or very low but fluctuated above or below the T(H)2-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(H)2-high and T(H)2-low endotypes.

【 授权许可】

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