Possible role of HE4 level elevation in the pathogenesis of TH2-high asthma

Abstract

Objectives

As a heterogeneous disease, asthma is characterized by airway hyperresponsiveness, airway inflammation, and airway mucus hypersecretion. According to the pathological changes, symptoms, preventive and treatment methods, asthma can be divided into TH2-high and TH2-low asthma. We show that the expression of the tumor biomarker human epididymis protein 4 (HE4) was significantly increased in TH2-high asthma group, while there was no marked difference in its expression between TH2-low asthma and healthy control groups. HE4 levels were significantly increased in plasma, induced sputum, and alveolar lavage fluid (BALF) samples and airway epithelial cells from TH2-high asthma group, showing that HE4 has a possible role in the pathogenesis of TH2-high asthma.

Methods

Using RT–qPCR, ELISA, Western blot (WB), and immunohistochemistry, we assessed differences in HE4 expression in plasma, induced sputum, BALF, and airway epithelial cells among patients with the TH2-related asthma subtypes and healthy controls. To explore the role of HE4 in TH2-high asthma, we conducted a correlation analysis between HE4 levels in plasma, induced sputum, BALF, and airway epithelial cells and multiple indicators of airway eosinophilic inflammation, airway mucus secretion, and airway remodeling.

Conclusion

We found for the first time that HE4 was differentially expressed in the TH2-related asthma subtypes. In TH2-high asthma, HE4 levels were markedly elevated in airway epithelial cells, plasma, induced sputum, and BALF. HE4 may play an important role in various pathogenic mechanisms of asthma, such as airway eosinophilic inflammation, airway mucus secretion, and airway remodeling. HE4 in plasma may be a clinically biomarker for differentiating TH2-related asthma subtypes.

Keywords:

• HE4
• TH2-high asthma
• airway eosinophil inflammation
• airway mucus secretion
• airway remodeling
• biomarker

Author contributions

Kan Zhang had full access to the data in the study and taken responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Kan Zhang and Yu Cao. Acquisition, analysis and interpretation of data: Kan Zhang, Yu Cao and Dang Lin. Drafting of the manuscript: Kan Zhang. Revising and polishing the manuscript: Hexuan Tang. Revision of the manuscript: Dang Lin. Statistical analysis: Kan Zhang. Supervision: Dang Lin. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (No. 82200031).