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Objective: Preliminary analysis of dynamic expression characteristics of plasma proteins in children with allergic asthma during subcutaneous immunotherapy (SCIT) with dust mite allergens based on multi-time-point proteomics technology. Methods: A cross-sectional study was conducted, enrolling 84 children with allergic asthma primarily sensitized to house dust mites (HDM) who visited the Children's Hospital of Soochow University between November 2024 and May 2025. Participants were categorized into five groups based on the duration of SCIT: 0M, 3M, 6M, 12M, and 24M. To detect the levels of specific immunoglobulin E (sIgE) and specific immunoglobulin G4 (sIgG4) against dust mite components (Der p1, Der f1, Der p2, Der f2, Der p5, Der p7, Der p10, Der p21, Der p23). Five subjects were randomly selected from each group using simple random sampling, and an additional 5 healthy children (HC) were included as the control group for plasma proteomic analysis. The temporal expression patterns of differentially expressed proteins were clustered via the Mfuzz algorithm and subjected to functional annotation. Results: A total of 84 children were enrolled, with a mean age of (10.12±2.15) years, including 57 males and 27 females. Statistically significant differences were observed in Der p1-, Der f1-, Der p2-, and Der f2-specific IgG4 levels among the five groups (all P<0.05). The 24M group exhibited significantly higher levels of Der p1-, Der f1-, Der p2-, and Der f2-specific IgG4 compared with the 0M group [Der p1: 695.20 (57.85, 1 894.60) vs 44.35 (32.10, 51.10); Der f1: 70.15 (51.35, 1 141.03) vs 46.65 (35.30, 63.68); Der p2: 3 440.20 (892.20, 4 183.00) vs 66.85 (43.08, 189.98); Der f2: 2 015.50 (704.60, 2 523.10) vs 69.10 (45.80, 159.35), all P<0.05]. Enrichment analysis of differentially expressed proteins in each group using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database showed that: compared with the healthy control group, the 0M group exhibited upregulation of cholesterol metabolism and complement/coagulation cascades, and downregulation of cornified envelope formation and ECM-receptor interaction pathways. compared with the 0M group, the 3M group showed upregulation of ECM-receptor interaction and focal adhesion and downregulation of fatty acid metabolism. The 6M group showed upregulation of cell adhesion molecules and downregulation of cholesterol metabolism; the 12M and 24M groups showed upregulation of TGF-β and PI3K-Akt pathways. Fuzzy C-means clustering analysis revealed that proteins highly expressed in the 6M group were enriched in glutathione metabolism, while those in the 24M group were significantly enriched in B cell-mediated immune responses. Six potential regulatory proteins (ARPC3, LPL, ILF3, FARSB, USP14, and SLIT2) were initially identified. Furthermore, Spearman correlation analysis revealed that ARPC3 was significantly negatively correlated with the levels of Der f2-sIgE, Der p2-sIgG4, and Der f2-sIgG4 (r=-0.44, -0.57, -0.54, respectively, all P<0.05). Additionally, ILF3 was positively correlated with Der p21-sIgE (r=0.57, P<0.01), FARSB was negatively correlated with Der p2-sIgG4 (r=-0.44, P<0.01), and USP14 was negatively correlated with Der f1-sIgE (r=-0.46, P<0.05). Conclusions: Differences exist in allergen antibody and plasma protein expression profiles among children with allergic asthma across groups with different durations of SCIT. The differentially expressed proteins may be involved in pathways related to airway epithelial barrier, metabolic homeostasis and immune regulation.