Eosinophil-associated gene signature expression in U-BIOPRED severe asthma

<b>Background:</b> Severe eosinophilic asthma is a phenotype of asthma associated with increased eosinophils in blood and sputum. <b>Objective:</b> Do eosinophil and anti-Interleukin (IL)-5/IL-5 receptor biologic gene signatures define different aspects of the severe asthma phenotypes? <b>Methods:</b> We used a gene signature from blood eosinophil upregulated transcripts in asthmatics and two anti-IL-5 antibody (benralizumab and mepolizumab)-derived gene signatures from blood and bronchoalveolar lavage cells, respectively, and used gene set variation analysis (GSVA) to calculate enrichment scores of these signatures in the blood, sputum and bronchial brushings transcripts of severe asthma. <b>Results:</b> The signatures were enriched in severe Type 2 (T2)-high asthma in bronchial brushings (Pavlidis, S. et al. Eur Respir J 2019; 53: 1800938) (Fig 1A-C). Enrichment of transcriptomic associated cluster (TAC)1 eosinophilic phenotype for all 3 signatures and of neutrophilic TAC2 (Kuo, C-HS. et al. Eur Respir J 2017 49: 1602135) for the mepolizumab signature is shown (Fig 1D-F). <b>Conclusions:</b> Use of these different signatures of eosinophil functionalities provides a more accurate phenotype of the eosinophilic severe asthma than an eosinophil blood count. This would explain the variable expression of these eosinophil signatures in the pauci-granulocytic TAC3.