Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma

Respiratory Research

Peter J. Sterk¹  Sven-Erik Dahlen²  Yike Guo³  Kai Sun³  Yusef Badi⁴  Ali Versi⁴  Nazanin Zounemat Kermani⁴  Kian Fan Chung⁴  Ian M. Adcock⁴  Ratko Djukanovic⁵  Peter Howarth⁵  Pank Bhavsar⁶  Woo-Jung Song⁷ 

[1] Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands;Centre for Allergy Research, Karolinska Institute, Stockholm, Sweden;Data Science Institute, Imperial College London, London, UK;Data Science Institute, Imperial College London, London, UK;National Heart and Lung Institute, Imperial College London, Dovehouse St, SW3 6LY, London, UK;Faculty of Medicine, Southampton University, Southampton, UK;NIHR Southampton Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK;National Heart and Lung Institute, Imperial College London, Dovehouse St, SW3 6LY, London, UK;National Heart and Lung Institute, Imperial College London, Dovehouse St, SW3 6LY, London, UK;Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea;

关键词: ACE2;    FURIN;    TMPRSS2;    Severe asthma;    Neutrophil;   

DOI  :  10.1186/s12931-020-01605-8

来源: Springer

【 摘 要 】

BackgroundPatients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells.MethodsWe examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels.ResultsACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes.ConclusionLevels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

【 授权许可】

CC BY