Immunological profiling of Chronic Obstructive Airways Disease and Idiopathic Pulmonary Fibrosis

Background: COPD and IPF are heterogeneous and complex conditions, which in some individuals coexist. Although their etiology is largely unknown and considered opposite, both have been associated with the presence of an abnormal immune response. The aim of this work was to characterize the similarities and differences of the lung and blood immune cell profile in IPF and COPD vs. normal lung function controls. Methods: To infer the lung infiltrate composition we used an immune cell deconvolution method in the microarray gene expression data from 582 subjects of the Lung Tissue Research Consortium: 160 IPF, 220 COPD and 108 controls. The whole dataset was split in two (test and validation cohort). We compared the differences in distribution of the immune cell signatures across diseases and assessed if these changes could be detected in blood by flow cytometry. Results: In lung, B-cell related signatures were up-regulated in IPF and severe COPD. IPF was also characterized by an up-regulation of activated CD4 and CD8 cell signatures. Alternatively, in severe COPD we observed an increase in CD8, Th1, Th17, macrophages, monocytes and dendritic signatures. Findings were replicated in the second dataset and validated by qPCR. In blood, we observed a significant decrease in CD8+ naive T cells in IPF and a trend toward lower levels of CD8+CD28+ cells in both IPF and COPD. Conclusions: IPF and COPD have shared and distinct immune profile abnormalities in the lung and blood, which might be underlying their co-occurrence and specific disease pathology.