Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma.
Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma.
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DOI：
10.1186/s12931-020-01605-8
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发表时间：
2021-01-07
影响因子：
5.8
通讯作者：
U-BIOPRED Consortium
中科院分区：
文献类型：
--
作者：
Kermani NZ;Song WJ;Badi Y;Versi A;Guo Y;Sun K;Bhavsar P;Howarth P;Dahlen SE;Sterk PJ;Djukanovic R;Adcock IM;Chung KF;U-BIOPRED Consortium
严重哮喘患者死于 COVID-19 疾病的风险可能更大。血管紧张素转换酶 2 (ACE2) 和蛋白酶、跨膜蛋白酶丝氨酸 2 (TMPRSS2) 和 FURIN 是病毒附着和侵入宿主细胞所必需的。我们检测了欧洲 U-BIOPRED 队列的痰液、支气管刷检和支气管活检中 ACE2、TMPRSS2 和 FURIN 的微阵列 mRNA 表达。检查临床参数和分子表型，包括哮喘严重程度、痰炎细胞、肺功能、口服皮质类固醇（OCS）的使用和转录组相关簇，与基因表达水平的关系。与轻中度哮喘相比，重度哮喘痰液中 ACE2 水平显着升高。在多变量分析中，痰 ACE2 水平与 OCS 使用和男性呈正相关。痰 FURIN 水平与中性粒细胞 (%) 和严重哮喘的存在显着相关。在支气管刷检样本中，TMPRSS2 水平与男性性别和体重指数呈正相关，而 FURIN 水平与男性性别和血液中性粒细胞呈正相关。在支气管活检中，TMPRSS2 水平与血液中性粒细胞呈正相关。以高炎症小体激活为特征的中性粒细胞分子表型在痰中表达的 FURIN 水平显着高于嗜酸性 2 型高或寡粒细胞氧化磷酸化表型。 ACE2 和 FURIN 的水平可能因哮喘的临床或分子表型而异。痰 FURIN 表达水平与中性粒细胞炎症和炎症小体激活密切相关。这可能表明中性粒细胞性严重哮喘中 SARS-CoV-2 感染可能导致更高的发病率和死亡率。
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. 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. 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. 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.
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影响因子：
24.3
作者：
Guan, Wei-jie;Liang, Wen-hua;He, Jian-xing
通讯作者：
He, Jian-xing
DOI：
10.1164/rccm.202003-0821oc
发表时间：
2020-07-01
影响因子：
24.7
作者：
Peters, Michael C.;Sajuthi, Satria;Fahy, John, V
通讯作者：
Fahy, John, V
DOI：
10.1164/rccm.202003-0541oc
发表时间：
2020-07-15
影响因子：
24.7
作者：
Zhang, Haijun;Rostami, Mahboubeh R.;Crystal, Ronald G.
通讯作者：
Crystal, Ronald G.
影响因子：
56.9
作者：
Yan, Renhong;Zhang, Yuanyuan;Zhou, Qiang
通讯作者：
Zhou, Qiang
影响因子：
82.9
作者：
Sungnak W;Huang N;Bécavin C;Berg M;Queen R;Litvinukova M;Talavera-López C;Maatz H;Reichart D;Sampaziotis F;Worlock KB;Yoshida M;Barnes JL;HCA Lung Biological Network
通讯作者：
HCA Lung Biological Network