Secondary Outcome: Differential Gene Expression in Blood Pre- Vs. Post-Benralizumab
Relevant blood DEGs between visit 2 (post-placebo) and visit 5 (post-benralizumab) samples include IDO1, PIK3R6, SIGLEC8, CYP4F12, IL5RA, ALOX15, and IL1R1 (S-Table 4) . These DEGs imply regulation by benralizumab of tryptophan metabolism, eosinophilic apoptosis, mast-cell mediator release and cytokine-signaling mediated by IL5R and IL1R1. Normalized expression levels of several of these DEGs correlated significantly with UAS7, eos% and CU-QoL Total Scores (S-Table 5 ). Additionally, several of these blood DEGs such as IDO1, PTGDR2, ALOX15, IL1RL1, and SLC29A1 may represent biomarkers that can distinguish complete responders from non-responders and partial responders. Interestingly, the predicted upstream regulator for all these genes, as determined by IPA, is IL4 32,33 suggesting that IL5-R antagonism may work through common pathways that also regulate IL4 activity such as through Nuclear Factor of Activated T-cells (NFAT).