High-dimensional characterisation of the airway wall of paediatric patients with asthma and pre-school wheeze using Imaging Mass Cytometry

Résumé fourni par la source

Recent evidence has shown that more than 1/3 of children with pre-school wheeze (PSW) progress to asthma, suggesting PSW may, in some cases, be a primary event in the development of asthma. Whilst unverified, remodelling of the airway wall, has been proposed as the intermediary between PSW and asthma. The scope of previous investigations has been limited by poor tissue availability and low-dimension imaging, preventing a holistic understanding of the diverse interactions between cells. Here we develop a highly multiplex Imaging Mass Cytometry (IMC) to spatially resolve airway remodelling in PSW and asthma. Archived formalin-fixed paraffin-embedded (FFPE) endobronchial biopsies obtained from children diagnosed with asthma (n=5), PSW (n=7) or disease controls with recurrent infections (DC; n=4) were employed in this study. A panel comprised of 23 markers directed to epitopes of the immune, epithelial, and stromal compartments were developed. IMC was carried out using the Hyperion Imaging System. This strategy enabled the identification of 10 cell types in each section. We identified the presence of an intraepithelial neutrophilhigh endotype, previously correlated with improved symptom control in 40% and 57% of asthmatic and PSW patients respectively. Despite this, upon neighbourhood analysis, significant associations between neutrophils and epithelial cells were only detected in the PSW cohort (0.3 a.u) and not asthma (-0.4 a.u). Overall, the robust pipeline established here will open the door to investigations with greater sample sizes, enabling the elucidation of novel interaction profiles including a progressive/protective endotype of PSW.

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