iTRAQ-based proteomic analysis reveals potential regulatory networks in dust mite-related asthma treated with subcutaneous allergen immunotherapy

Abstract

Asthma is one of the most common childhood chronic diseases worldwide. Subcutaneous immunotherapy (SCI T) is commonly used in the treatment of house dust mite (HDM)-related asthma in children. However, the therapeutic mechanism of SCI T in asthma remains unclear. The present study aimed to investigate the molecular biomarkers associated with HDM-related asthma in asthmatic children prior and subsequent to SCI T treatment compared with those in healthy children via proteomic analysis. The study included a control group (30 healthy children), -Treatment group (30 children with HDM-related allergic asthma) and +Treatment group (30 children with HDM-related allergic asthma treated with SCI T). An isobaric labeling with relative and absolute quantification-based method was used to analyze serum proteome changes to detect differentially expressed proteins, while functional enrichment and protein-protein interaction network analysis were used to select candidate biomarkers. A total of 72 differentially expressed proteins were detected in the -Treatment, +Treatment and control groups. A total of 33 and 57 differentially expressed proteins were observed in the -Treatment vs. control and +Treatment vs. control groups, respectively. Through bioinformatics analysis, 5 candidate proteins [keratin 1 (KRT1), apolipoprotein B (APOB), fibronectin 1, antithrombin III (SER PINC 1) and α-1-antitrypsin (SER PINA 1)] were selected for validation by western blotting; among them, 4 proteins (KRT1, APOB, SER PINC 1 and SER PINA 1) showed robust reproducibility in asthma and control samples. This study illustrated the changes in proteome regulation following SCI T treatment for asthma. The 4 identified proteins may serve as potential biomarkers prior and subsequent to SCI T treatment, and help elucidate the molecular regulation mechanisms of SCI T to treat HDM-related asthma.