Metabolic and Cellular Characterization of Severe Asthma
Objective Asthma is a common chronic inflammatory airway disease,and severe asthma poses a significant challenge in its diagnosis and management.Immune cells are involved in and altered by asthma pathogenesis,and several lipid metabolites can serve as diagnostic markers for the disease.In this study,we investigated the characterization of severe asthma at the metabolic and cellular level.Methods Differential metabolites in blood samples from severe asthma(41 cases)and controls(18 cases)were screened using multifactorial statistical analysis and independent samples t-tests;key pathways were identified by KEGG enrichment analysis,and biomarkers were characterized based on ROC curves;immune cell types and proportions in the blood were identified based on the results of cell-type annotations(5 severe and 3 control cases);and single-sample Gene Enrichment Analysis(ssGSEA)to investigate the characterization of differential metabolic pathways in single cells.Results Compared with controls,the abundance of 28 metabolites was increased and the abundance of 13 metabolites was decreased in the blood of patients with severe asthma(P＜0.05);the differential metabolites were enriched in 4 pathways:sphingolipid metabolism,glycerophospholipid metabolism,nicotinate and nicotinamide metabolism,and histidine metabolism.Among them,13 differential metabolites could be used as biomarkers for the diagnosis of severe asthma,including L-glutamic acid(AUC=0.809),nicotinamide(AUC=0.886),phytosphingosine(AUC=0.882),and sphinganine(AUC=0.893).In single-cell transcriptome analysis,5 key cell types were identified:CD4+T cells,CD8+T cells,NK cells,B cells,and monocytes.The number of NK cells was increased in patients with severe asthma,and severe asthma exhibited more frequent cellular communication,particularly dense communication between CD8+T cells and other cell types.In healthy samples,monocytes were the primary cells engaging in dense communication.Single-sample gene enrichment analysis(ssGSEA)showed that 4 pathways enriched for differential metabolites had lower scores(P＜0.01)in CD4+T and CD8+T cells in severe patients,and it was hypothesized that the expression of genes associated with these pathways was suppressed in these two types of cells.The suppressed genes included DGKA and NT5C3A,which are associated with immune processes.We observed that these genes play key roles in the regulation of T cell signaling,activation,differentiation,and immune responses.Conclusion L-glutamic acid,nicotinamide,phytosphingosine,and sphinganine can be used as biomarkers for the diagnosis of severe asthma;genes of the severe asthma-associated pathway were suppressed in CD4+T cells and CD8+T cells.
severe asthmametabolomesingle-cell transcriptomebiomarkerscell type
万方数据
维普
