RT Journal Article
SR Electronic
T1 An interferon-inducible signature of airway disease from blood gene expression profiling
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2100569
DO 10.1183/13993003.00569-2021
VO 59
IS 5
A1 Yun, Jeong H.
A1 Lee, Sool
A1 Srinivasa, Pooja
A1 Morrow, Jarrett
A1 Chase, Robert
A1 Saferali, Aadbida
A1 Xu, Zhonghui
A1 Cho, Michael
A1 Castaldi, Peter
A1 Hersh, Craig P.
YR 2022
UL https://publications.ersnet.org//content/59/5/2100569.abstract
AB Background The molecular basis of airway remodelling in chronic obstructive pulmonary disease (COPD) remains poorly understood. We identified gene expression signatures associated with chest computed tomography (CT) scan airway measures to understand molecular pathways associated with airway disease.Methods In 2396 subjects in the COPDGene Study, we examined the relationship between quantitative CT airway phenotypes and blood transcriptomes to identify airway disease-specific genes and to define an airway wall thickness (AWT) gene set score. Multivariable regression analyses were performed to identify associations of the AWT score with clinical phenotypes, bronchial gene expression and genetic variants.Results Type 1 interferon (IFN)-induced genes were consistently associated with AWT, square root wall area of a hypothetical airway with 10 mm internal perimeter (Pi10) and wall area percentage, with the strongest enrichment in AWT. A score derived from 18 genes whose expression was associated with AWT was associated with COPD-related phenotypes including reduced lung function (forced expiratory volume in 1 s percentage predicted β= −3.4; p<0.05) and increased exacerbations (incidence rate ratio 1.7; p<0.05). The AWT score was reproducibly associated with AWT in bronchial samples from 23 subjects (β=3.22; p<0.05). The blood AWT score was associated with genetic variant rs876039, an expression quantitative trait locus for IKZF1, a gene that regulates IFN signalling and is associated with inflammatory diseases.Conclusions A gene expression signature with IFN-stimulated genes from peripheral blood and bronchial brushings is associated with CT AWT, lung function and exacerbations. Shared genes and genetic associations suggest viral responses and/or autoimmune dysregulation as potential underlying mechanisms of airway disease in COPD.Airway wall thickness in chronic obstructive pulmonary disease (COPD) is associated with type 1 interferon signalling from peripheral blood gene expression https://bit.ly/2WEjvFH