Chronic Obstructive Pulmonary Disease-Specific Gene Expression Signatures of Alveolar Macrophages as well as Peripheral Blood Monocytes Overlap and Correlate with Lung Function

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by progressive airflow limitation and significant extrapulmonary (systemic) effects that lead to co-morbid conditions, though the pathomechanism of COPD is largely undetermined. Alveolar macrophages (AM) derived from peripheral monocytes (MO) appear to play a key role in initiating and/or sustaining disease progression. Objectives: To identify disease- and cell type-specific gene expression profiles and potential overlaps in those in order to diagnose COPD, characterize its progression and determine the effect of drug treatment. Method: Global gene expression analysis was used for primary screening in order to obtain expression signatures of AMs and circulating MOs of COPD patients and healthy controls. The results of microarray analyses of AMs (20 controls and 26 COPD patients) and MOs (16 controls and 22 COPD patients) were confirmed and validated by real-time quantitative polymerase chain reaction. Results: We have identified gene sets specifically associated with COPD in AMs and MOs. There were overlapping genes between the two cell types. Our data also show that COPD-specific gene expression signatures in AMs and MOs correlate with percent of predicted FEV₁. Conclusion: Disease-specific and overlapping gene expression signatures can be defined in lung-derived macrophages and also in circulating monocytes. Some of the validated expression changes in both cell types correlate with lung function and therefore could serve as biomarkers of disease progression.

Integrative genomics of chronic obstructive pulmonary disease

“…Poliska et al found overlapping genes expressed in blood monocyte and alveolar macrophages in a limited number of COPD cases and controls. [70] Bhattacharya et al compared peripheral blood mononuclear cell expression profiles to their previous study of lung tissue,[16] finding several genes with similar expression results across the two tissues. [71] The lung-blood expression relationships found in the latter two studies show that peripheral blood can be used for COPD genomics studies.…”

Meta-analysis of peripheral blood gene expression modules for COPD phenotypes

“…The rationale for using blood to study COPD is increasing evidence that COPD is a systemic disease [9], with several systemic biomarkers associated with exacerbation of COPD (see [2] and references therein). Several studies of blood from COPD subjects have suggested that there are genomic signatures associated with COPD (see [2, 10, 11] and references therein). These studies were limited in that they were also of small sample size, did not have replications, and tended to examine individual genes in isolation.…”

The Effect of Different Case Definitions of Current Smoking on the Discovery of Smoking-Related Blood Gene Expression Signatures in Chronic Obstructive Pulmonary Disease

“…10,11 Many blood gene expression profiling studies have been published for COPD. [12][13][14][15] Smoking is an important driver and confounder of these studies. The studies typically compare the genome-wide expression profiles between COPD cases and smoking controls, and include self-reported smoking status and/ or pack-years as covariates in the analysis.…”