Sputum Gene Expression of IL-13 Receptor α₂ Chain Correlates with Airflow Obstruction and Helper T-Cell Type 2 Inflammation in Asthma

Abstract

Background: BRP-39/YKL-40 is a chitinase-like protein that plays a critical role in IL-13–induced inflammation. It correlates positively with asthma severity and airway remodeling (1) via binding to IL-13 receptor α₂ chain (IL-13Rα2). Because the relationship of IL-13Rα2 to human asthma has never been evaluated previously, we sought to determine the relationship between IL-13Rα2, YKL-40, and asthma.

Methods: We evaluated 112 patients (69% women) with a mean age of 46.7 years. Subjects completed an asthma phenotyping protocol that included analysis of sputum gene expression by Affymetrix 1.0 ST gene array (Affymetrix, Santa Clara, CA) and YKL-40 protein levels.

Measurements and Main Results: IL-13Rα2 gene expression was readily detectable in the sputum and correlated negatively with prebronchodilator (BD) FEV₁ (r_s = −0.282, P < 0.01), post-BD FEV₁ (r_s = −0.268, P < 0.01), pre-BD FEV₁/FVC ratio (r_s = −0.228, P < 0.05), and post-BD FEV₁/FVC ratio (r_s = −0.242, P < 0.01). IL-13Rα2 gene expression correlated positively with gene expression of IL-13 (r_s = 0.484, P < 0.001), IL-5 (r_s = 0.237, P < 0.05), and IL-8 (r_s = 0.218, P < 0.05). Regression analysis showed that the post-BD FEV₁/FVC ratio is significantly associated with IL-13Rα2 expression and CHI3L1 expression in sputum after controlling for IL-4, IL-5, IL-13, and transforming growth factor-β₁ gene expression (all P < 0.01). Sputum YKL-40 gene expression positively correlated with IL-8 expression (r_s = 0.357, P < 0.001) and negatively correlated with pre- and post-BD FEV₁/FVC ratios (r_s = −0.299, P < 0.001 and r_s = −0.305, P < 0.01, respectively). Sputum and serum YKL-40 protein levels were not associated with IL-13Rα2 expression.

Conclusions: This analysis demonstrates that IL-13Rα2 is associated with reduced lung function, helper T-cell type 2 gene expression, and airflow obstruction in the airway of individuals with asthma, which might in turn be driven by airway remodeling. Future studies will be required to define the proinflammatory and remodeling effects of this receptor that up to now has been considered solely a modulator of IL-13–induced inflammation.