Journal Article

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

Howarth, Peter, Chung, Kian Fan, Bhavsar, Pank, Adcock, Ian M., Guo, Yike, Djukanovic, Ratko, Badi, Yusef, Kermani, Nazanin Zounemat, Dahlen, Sven-Erik, Sterk, Peter J., Versi, Ali, Sun, Kai, Song, Woo-Jung

2021

Overview

Background Patients 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. Methods We 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. Results ACE2 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. Conclusion Levels 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.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: ACE2 / Adult / Allergens / Angiotensin / Angiotensin converting enzyme / Angiotensin-converting enzyme 2 / Angiotensin-Converting Enzyme 2 - biosynthesis / Angiotensin-Converting Enzyme 2 - genetics / Asthma / Asthma - enzymology / Asthma - epidemiology / Asthma - genetics / Biopsy / Blood / Body mass index / Body size / Brushing / Cohort Studies / Complications and side effects / Coronaviruses / Corticosteroids / COVID-19 / COVID-19 - enzymology / COVID-19 - epidemiology / COVID-19 - genetics / DNA microarrays / Enzymes / Female / FURIN / Furin - biosynthesis / Furin - genetics / Gender / Gene expression / Genetic aspects / Health aspects / Humans / Infections / Inflammasomes / Inflammation / Leukocytes (eosinophilic) / Leukocytes (neutrophilic) / Male / Medicine / Medicine & Public Health / Middle Aged / Morbidity / Multivariate analysis / Neutrophil / Neutrophils / Neutrophils - enzymology / Oxidative phosphorylation / Peptidyl-dipeptidase A / Phenotypes / Phosphorylation / Pneumology/Respiratory System / Prognosis / Proteases / Regression analysis / Respiratory function / Serine / Serine Endopeptidases - biosynthesis / Serine Endopeptidases - genetics / Severe acute respiratory syndrome coronavirus 2 / Severe asthma / Severity of Illness Index / Smoking / Sputum / Sputum - enzymology / TMPRSS2 / Viral diseases / Virus attachment