LSC Abstract – The use of microarray analysis of gene signalling to determine heterogeneity of COPD exacerbation phenotypes

Abstract

Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogenous with respect to aetiology, inflammatory pathways and inflammation severity. This study was designed to investigate one of the most fundamental paradigms; during inflammatory episodes, affected tissues “signal” to central lymphoid organs in order to initiate adaptive and innate responses. Evidence based on transcriptomic profiling indicates that this process involves functional programming of migratory immune cells before their release into circulation. Different inflammatory triggers induce the release of different combinations of molecular mediators, and recognition of these mediators by myeloid and lymphoid precursors induces up-regulation of discrete groups of expressed genes. In exacerbations of COPD, identification of gene signalling in migrating immune cell populations has the potential to reveal new drug targets to control exacerbation progression. Through analysis of genome wide expression profiling of paired peripheral blood mononuclear cells (PBMC) samples collected during COPD exacerbations, compared to post convalescent samples, this study has suggested the existance of three distint COPD exacerbator subgroups, as defined by exacerbation-associated expression phenotypes, namely T-cell predominant, innate cell predominant, and a third pauci-immune subgroup (figure 1) COPD exacerbation responses in PBMCs are characterised by three major molecular phenotypes. Yellow/blue colour schemes indicate high/low expression in Figure 1