Spatial profiling reveals complex inflammatory responses of anti-IL5
treatment with mepolizumab in eosinophilic chronic rhinosinusitis with
nasal polyposis
Abstract
Background: There is limited understanding of the impact of anti-IL5
treatment on nasal polyp tissue biology in chronic rhinosinusitis with
nasal polyps (CRSwNP). The aim of this study was to determine the effect
of the nasal polyp tissue cellular proteome and transcriptome in
response to six months of anti-IL5 treatment with mepolizumab in CRSwNP
utilising high-plex spatial profiling. Methods: GeoMx™ Digital Spatial
Profiling (DSP) of 80 proteins and 1,833 mRNA targets in the polyp
stroma and of the whole transcriptome (18,815 mRNA targets) in polyp
epithelia was undertaken on formalin-fixed paraffin embedded slides of
sinonasal biopsies collected before and after 16 and 24 weeks of
treatment with mepolizumab. Results: Anti-IL5 therapy with mepolizumab
in patients with eosinophilic CRSwNP had significant tissue biological
impact. Treatment-related changes in proteins within immune checkpoint
inhibition, neutrophil degranulation and the innate immune system were
key biological mechanisms identified in a protein interaction network.
Transcriptionally, there were significant reductions in gene sets
associated with the reactome terms innate and adaptive immune system,
neutrophil degranulation and TGFβ receptor signalling in epithelial to
mesenchymal transition within polyp stroma, as well as enhancing
antioxidant pathways. In polyp epithelia, increases in gene sets
associated with the reactome-terms cilium assembly and keratinisation
and a reduction in the regulation of KIT signalling were observed with
treatment. Conclusions: Spatial profiling technology demonstrates that
the effects of anti-IL5 treatment within nasal polyp tissue extend well
beyond simple eosinophil reduction to broader regulation of innate and
adaptive immune cells and in improving the epithelial barrier biology.