Expression of eosinophil-associated gene signatures in U-BIOPRED severe asthma

<b>Background:</b> Patients with severe eosinophilic asthma have high sputum and blood eosinophil counts and benefit from anti-interleukin (IL)-5 therapy. <b>Objective:</b> To determine the characteristics of the severe eosinophilic asthma phenotype in the U-BIOPRED asthma cohort defined by eosinophil-associated gene signatures. <b>Method:</b> A gene signature of blood eosinophil upregulated genes in asthmatics and two anti-IL-5 therapy derived gene signatures from blood and bronchoalveolar lavage cells, (Barnig et al. PLoS ONE 2015 10(11): e0141740; Sridhar et al. Respiratory Research 2019 20:14) were analysed by gene set variation analysis (GSVA) to calculate enrichment scores (ESs) in the blood, sputum and bronchial brushings transcriptomics. <b>Results:</b> The three gene signatures were enriched in severe Th2 high asthma (p&lt;0.05) but show distinct patterns. Hierarchical clustering of ESs showed the most enriched group is associated with increased sputum eosinophil counts (5.68 v 1.15 %), FENO (54 v 20 ppb) IgE (153.35 v 95.6 IU/L) and IL-13 (1.01 v 0.37 pg/ml; all p&lt;0.05) compared to the low enrichment group (Fig 1). Pathway analysis of upregulated DEGs in the most enriched group was associated with FGFR2, IL-33 and insulin signalling pathways. <b>Conclusion:</b> This transcriptomic approach identifies patients associated with severe eosinophilic asthma as most likely potential responders to anti-IL-5/5R therapy and displays a phenotype beyond eosinophil counts.