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).