The present study aims to provide novel targets and translational evidence for pediatric allergic rhinitis (AR) immunotherapy, offering potential for personalized intervention strategies. This study utilized bulk and scRNA-seq datasets. Gene co-expression networks were constructed via weighted gene co-expression network analysis (WGCNA). Differential expression analysis between AR and control groups used limma to identify DEGs. LASSO regression (glmnet) and SVM-RFE (e1071) refined DEGs, with intersecting genes as candidate biomarkers. Immune cell infiltration was quantified via CIBERSORT. ssGSEA calculated enrichment scores. Enrichr predicted potential drugs targeting biomarkers. Cell type-specific marker genes were identified via FindAllMarkers. For in vitro validation, HMC-1 cells were treated with C48/80, measuring mRNA expression of IL-4, IL-13, TNF-α and IFN-γ via qRT-PCR. This study identified two core pediatric AR biomarkers: Cystatin SN ( CST1 ) and Thymocyte Selection-Associated High Mobility Group Box Protein ( TOX ). These DEGs correlated strongly with immune cell infiltration and immunity/inflammation pathways. At single-cell level, CST1 localized to epithelial/goblet cells, TOX to T cells. Molecular docking showed retinoic acid binds both proteins well. In vitro AR models had elevated IL-4, IL-13, TNF-α and reduced IFN-γ . This study identifies CST1 and TOX as key immune biomarkers for pediatric allergic rhinitis, explores their roles in immune cell infiltration and pathology, and predicts retinoic acid as a targeted therapeutic agent via bioinformatics. This study validated CST1 and TOX as pivotal biomarkers in childhood AR. The findings provide critical clues for future advancement of precision diagnosis and targeted therapies.
Xiao et al. (Wed,) studied this question.