囊性纤维化
伊瓦卡夫托
囊性纤维化跨膜传导调节器
炎症
免疫学
医学
吞噬作用
巨噬细胞
先天免疫系统
免疫系统
内科学
生物
体外
生物化学
作者
Shuzhong Zhang,Chandra L. Shrestha,Frank Robledo‐Avila,Devi Jaganathan,B Wisniewski,Nevian Brown,Hanh Thi Pham,Katherine Carey,Amal O. Amer,Luanne Hall-Stoodley,Karen McCoy,Shasha Bai,Santiago Partida-Sánchez,Benjamin T. Kopp
出处
期刊:The European respiratory journal
[European Respiratory Society]
日期:2022-10-20
卷期号:61 (4): 2102861-2102861
被引量:16
标识
DOI:10.1183/13993003.02861-2021
摘要
Background Abnormal macrophage function caused by dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) is a critical contributor to chronic airway infections and inflammation in people with cystic fibrosis (PWCF). Elexacaftor/tezacaftor/ivacaftor (ETI) is a new CFTR modulator therapy for PWCF. Host–pathogen and clinical responses to CFTR modulators are poorly described. We sought to determine how ETI impacts macrophage CFTR function, resulting effector functions and relationships to clinical outcome changes. Methods Clinical information and/or biospecimens were obtained at ETI initiation and 3, 6, 9 and 12 months post-ETI in 56 PWCF and compared with non-CF controls. Peripheral blood monocyte-derived macrophages (MDMs) were isolated and functional assays performed. Results ETI treatment was associated with increased CF MDM CFTR expression, function and localisation to the plasma membrane. CF MDM phagocytosis, intracellular killing of CF pathogens and efferocytosis of apoptotic neutrophils were partially restored by ETI, but inflammatory cytokine production remained unchanged. Clinical outcomes including increased forced expiratory volume in 1 s (+10%) and body mass index (+1.0 kg·m −2 ) showed fluctuations over time and were highly individualised. Significant correlations between post-ETI MDM CFTR function and sweat chloride levels were observed. However, MDM CFTR function correlated with clinical outcomes better than sweat chloride. Conclusion ETI is associated with unique changes in innate immune function and clinical outcomes.
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