J Korean Med Sci.  2022 Feb;37(8):e65. 10.3346/jkms.2022.37.e65.

Soluble ACE2 and TMPRSS2 Levels in the Serum of Asthmatic Patients

• Lee JH
• Lee CE
• Yoo Y
• Shin E
• An J
• Park SY
• Song WJ
• Kwon HS
• Cho YS
• Moon HB
• Kim TB

• KMID: 2526797
• DOI: http://doi.org/10.3346/jkms.2022.37.e65

Abstract

Background
Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics.
Methods
Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed.
Results
The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2.
Conclusion
The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients.

Keyword

Angiotensin-Converting Enzyme 2; Transmembrane Protease Serine Subtype 2; COVID-19; Asthma

Figure

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  Fig. 1 Relationship between ACE2 levels and clinical variables. The level of ACE2 were compared between subgroups according to age (A), BEC (B), and ICS use (C).ACE2 = angiotensin-converting enzyme 2, BEC = blood eosinophil count, ICS = inhaled corticosteroids.

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  Fig. 2 Correlation between ACE2 and eosinophilic inflammatory markers. The correlation between ACE2 and eosinophilic inflammatory markers including BEC (A) and FeNO (B).ACE2 = angiotensin-converting enzyme 2, BEC = blood eosinophil count, FeNO = fractional exhaled nitric oxide.

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  Fig. 3 Relationship between TMPRSS2 levels and clinical variables. The level of TMPRSS2 were compared between subgroups according to age (A), sex (B), smoking history (C), BEC (D), FEV1/FVC (E), and presence of HTN (F).TMPRSS2 = transmembrane protease serine subtype 2, BEC = blood eosinophil count, FEV1 = forced expiratory volume in 1 second, FVC = forced vital capacity, HTN = hypertension.

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  Fig. 4 Correlation between TMPRSS2 and sputum neutrophils. The correlation between TMPRSS2 and percentage of sputum neutrophils.TMPRSS2 = transmembrane protease serine subtype 2.

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