Transcriptomics in T2-high severe asthmatics treated with biologics: Comparison between anti-IgE, anti-IL-5 and anti-IL-5R-targeted treatments.

Background : Biologic therapies have transformed severe asthma management, particularly for T2-high asthma. We aimed to investigate blood proteomics and transcriptomics after biologic treatment. Methods : A prospective study was conducted on 35 patients with severe T2-high asthma treated with mepolizumab (n=9), benralizumab (n=14), or omalizumab (n=12). Evaluations occurred at baseline and after 16 weeks (omalizumab) or 24 weeks (mepolizumab, benralizumab) of treatment. Blood samples were collected. Gene expression was analyzed via Illumina TruSeq RNA Prep, with RNA sequencing on the Illumina NovaSeq-6000 platform. Results : RNA-seq analysis revealed 86 down-regulated genes common to both mepolizumab and benralizumab, primarily associated with eosinophils, basophils, and the purinergic receptor signaling pathway. Additionally, there was evidence of gene regulation involved in antiviral immunity. However, specific gene modulation was observed for benralizumab (114 genes) and mepolizumab (68 genes). Changes following omalizumab treatment were minimal, with only three significantly down-regulated genes. Conclusion : While omalizumab showed minimal quantifiable effects on gene expression, mepolizumab and benralizumab—despite exhibiting distinct profiles—both induced down-regulation of genes related to eosinophil and basophil biology and purinergic signaling pathways, alongside up-regulation of genes involved in innate antiviral immunity. Overall design: RNA-seq profiling to assess the modifications of blood inflammatory signals and inflammatory cell profile in samples collected at baseline and after 16-24 weeks of treatment in severe asthmatic patients.