Th2 subsetting of U-BIOPRED asthma subjects based on airway transciptomic profiles

We hypothesized that Gene Set Variation Analysis (GSVA) of gene expression in bronchial brushings can effectively classify airway Th2-high status in U-BIOPRED asthmatics. Airway Th2-status was defined as IL-13-induced transcriptional activity, evaluated as enrichment of IL-13 in-vitro stimulation (IVS) or expression of POSTN and SERPINB2 in human bronchial epithelial cell transcriptomic profiles from U-BIOPRED asthma patients. Based on IL-13 IVS GSVA enrichment scores above the 95 th percentile for healthy subjects, 53% of severe asthma (SA) non-smokers (n=49), 67% of SA smokers (n=18) and 36% of non-severe asthmatics (n=36) were classified as Th2-high. Eosinophilic inflammation marker values are shown in Figure 1. Using the mean normalised expression of POSTN and SERPINB2 as an alternative Th2 stratification factor, 35% of SA non-smokers, 22% of SA smokers, and 14% of non-severe asthmatics were Th2-high, mostly subsets of the IL-13 IVS-defined Th2-high asthma groups and consistent with the modest correlation (r=0.39) between the IL-13 IVS enrichment scores and POSTN/SERPINB2 scores. IL-13 IVS and POSTN/SERPINB2 based definitions of Th2 activity showed associations with eosinophilic and atopy markers, with good agreement for Th2-high vs. -low calls, although the latter approach may be too conservative. IL-13 IVS enrichment identified a broader set of subjects with airway Th2 activity when compared to POSTN and SERPINB2. Funded by IMI.