Transcriptomic profiling of pediatric asthma by diseases state and severity

Despite the high prevalence of pediatric asthma, the molecular basis of its pathogenesis remains incompletely understood, in part due to the complex and heterogeneous nature of the disease. In this study, we performed bulk RNA sequencing of peripheral blood mononuclear cells (PBMCs) from 183 children (114 asthma cases, 69 controls) across two independent cohorts as a minimally invasive approach to capture the gene expression changes underlying asthma status and severity. Our analysis identified robust signatures of pediatric asthma, including differential expression of a canonical asthma gene ( RAB7B ) and two novel genes ( RPP38-DT , NCAL1 ), which encode long non-coding RNAs. Additionally, severity-stratified analyses revealed upregulation of several immune-related genes ( CCL8 , ACOD1 , CXCL9 , SLAMF1 , EPN2 ) and downregulation of an uncharacterized transcript ( ENSG00000288973 ) as asthma severity increased. Enrichment and co-expression analysis further implicate impaired type I interferon signaling in asthma disease severity. Our results demonstrate contributions to the pathobiology of asthma among several novel molecular candidate genes, which may support future efforts towards molecular stratification of pediatric asthma.