Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Gangneung Asan Hospital, Gangneung, Korea.
J Korean Med Sci. 2022 Feb 28;37(8):e65. doi: 10.3346/jkms.2022.37.e65.
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.
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.
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.
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.
血管紧张素转换酶 2（ACE2）和跨膜丝氨酸蛋白酶 2 型（TMPRSS2）是介导严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）病毒进入的关键蛋白。虽然 ACE2 和 TMPRSS2 的基因表达已在各种器官和疾病中进行了分析，但它们的可溶性形式研究较少，特别是在哮喘中。因此，我们旨在测量哮喘患者血清中的循环 ACE2 和 TMPRSS2，并研究它们与临床特征的关系。
从哮喘队列中获得了 400 名参与者的临床数据和血清样本。通过酶联免疫吸附试验测量可溶性 ACE2（sACE2）和可溶性 TMPRSS2（sTMPRSS2）水平，并对数值进行自然对数转换。分析了 sACE2 和 sTMPRSS2 水平与各种临床变量之间的关系。
年龄小于 70 岁、嗜酸性粒细胞性哮喘（嗜酸性粒细胞≥200 个/µL）和未使用吸入皮质类固醇（ICS）的患者与较高的 sACE2 水平相关。血嗜酸性粒细胞和呼出气一氧化氮分数与血清 ACE2 呈正相关。相反，年龄小于 70 岁和嗜酸性粒细胞性哮喘患者的 sTMPRSS2 水平较低，而 ICS 使用与 sTMPRSS2 之间无关联。sTMPRSS2 的水平也根据性别、吸烟史、并存高血压和 1 秒用力呼气量/用力肺活量（FEV1/FVC）比值而有所不同。痰中性粒细胞比例与 sTMPRSS2 呈正相关，而 FEV1/FVC 比值与 sTMPRSS2 呈负相关。
ACE2 和 TMPRSS2 的水平根据年龄、ICS 使用和几种炎症标志物的不同而有所表达。这些发现表明哮喘患者对 SARS-CoV-2 感染的易感性和预后存在差异。
