Single-cell RNA sequencing reveals immunological link between house dust mite allergy and childhood asthma

Allergic asthma in children is typically associated with house dust mites (HDM) as the key allergen. Nevertheless, the diagnostic rate remains below 60% due to the absence of specific symptoms and diagnostic markers, which hinders the implementation of targeted personalized therapies. This study investigates immunological features of asthma with house dust mite (HDM) sensitisation in children, aiming to uncover diagnostic markers at single-cell resolution. The cohort comprised 8 children with physician-diagnosed asthma (age range: 4-11 years), stratified into groups based on HDM sensitization status. Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) was conducted, employing Seurat for cell identification and differential gene expression analysis. Enrichment analyses and LASSO regression identified signature genes related to cellular origin, with protein-protein interaction networks elucidating cellular communication differences between groups. A total of 11 distinct cell types were identified, with classical monocytes and monocytes being the predominant cell types that differentiated the two groups. Among these, 12 genes were up-regulated, and 40 down-regulated, mainly involving MHC-II complex and antigen presentation pathways, as validated by Gene Ontology and Gene Set Enrichment Analysis. The machine learning model accurately predicted cellular groupings, evidenced by an area under the curve of 0.83. Enhanced communication signals in HDM allergy cases involved monocytes, contrasting with reduced interactions in naive CD8 + cells. HLA-DR and HLA-DP were identified as the primary hallmark receptors, and the innate immunity differences with non-dust mite allergic asthma were characterized by 18 genes including top candidates MT-ND4 and RPS3A. Individuals with HDM-sensitized asthma exhibited altered expression of MHC-II complex genes in their PBMCs and distinct gene expression patterns in antigen-presenting cells, highlighting the critical role of HLA-DR and HLA-DP in the HDM allergen presentation.