儿童过敏性哮喘SCIT治疗前后2型炎症关键 基因的表达变化与疗效分析

Expression Changes and Efficacy Analysis of Key Genes Related to Type 2 Inflammation in Children with Allergic Asthma before and after SCIT Treatment

摘要: 目的：本研究旨在探讨皮下特异性免疫治疗(subcutaneous immunotherapy, SCIT)对哮喘患儿外周血单个核细胞(peripheral blood mononuclear cells, PBMC)中2型炎症通路关键基因表达的影响，并分析其与临床疗效的相关性，筛选潜在疗效评估生物标志物。方法：本研究纳入了30例接受SCIT的过敏性哮喘患儿，于治疗前及治疗16周后收集其临床资料及PBMCs，通过qRT-PCR检测PBMCs中IL-4、IL-5、IL-13等13个2型炎症通路关键基因的mRNA表达水平，通过配对t检验、Spearman秩相关分析等方法，分析基因表达与临床评分、肺功能指标的相关性。结果：与基线组相比，SCIT治疗16周组患儿ACQ、CSMS评分下降、C-ACT评分上升、PEF上升(P < 0.05)，FEV₁无显著变化(P > 0.05)；PBMCs中GATA3、IL-13的mRNA表达水平下降(P < 0.05)，其余11个基因表达水平差异无统计学意义(P > 0.05)。相关性分析进一步表明，基线期GATA3、IL-13 mRNA表达水平与治疗16周后临床指标的改善程度ΔACQ、ΔCSMS评分呈正相关，ΔC-ACT评分、ΔPEF及ΔFEV₁呈负相关(P < 0.05)。结论：SCIT可通过抑制尘螨过敏性哮喘患儿PBMC中2型炎症通路转录调控因子GATA3及效应因子IL-13的基因表达发挥早期治疗作用，且该基因变化与临床症状、肺功能改善密切相关，提示GATA3、IL-13有望成为评估SCIT早期疗效的潜在候选生物标志物。未来需扩大样本量、开展长期随访并补充蛋白水平验证，以完善机制阐释并验证其远期预测价值与临床应用。

Abstract: Objective: This study aims to investigate the impact of subcutaneous immunotherapy (SCIT) on the expression of key genes in the type 2 inflammation pathway in peripheral blood mononuclear cells (PBMCs) of children with asthma, analyze its correlation with clinical efficacy, and screen potential biomarkers for evaluating therapeutic effectiveness. Methods: This study included 30 children with allergic asthma undergoing SCIT. Clinical data and PBMCs were collected before and after 16 weeks of treatment. The mRNA expression levels of 13 key genes in the type 2 inflammation pathway, including IL-4, IL-5, and IL-13, in PBMCs were detected by qRT-PCR. The correlation between gene expression and clinical scores, pulmonary function indicators was analyzed using paired t-tests and Spearman rank correlation analysis. Results: Compared with the baseline group, the 16-week SCIT group showed decreased ACQ and CSMS scores, increased C-ACT score, and increased PEF (P < 0.05), while FEV₁ showed no significant change (P > 0.05). The mRNA expression levels of GATA3 and IL-13 in PBMCs decreased (P < 0.05), while there were no statistically significant differences in the expression levels of the remaining 11 genes (P > 0.05). Further correlation analysis indicated that the baseline mRNA expression levels of GATA3 and IL-13 were positively correlated with the improvement in clinical indicators after 16 weeks of treatment, specifically ΔACQ and ΔCSMS scores, and negatively correlated with ΔC-ACT score, ΔPEF, and ΔFEV₁ (P < 0.05). Conclusion: SCIT exerts early therapeutic effects by inhibiting the gene expression of GATA3, a transcriptional regulator of the type 2 inflammation pathway, and IL-13, an effector factor, in PBMCs of children with dust mite allergic asthma. These gene changes are closely related to clinical symptom improvement and pulmonary function enhancement, suggesting that GATA3 and IL-13 may serve as potential biomarkers for evaluating the early efficacy of SCIT. Future studies should expand the sample size, conduct long‑ term follow‑up, and supplement protein level verification to improve mechanistic interpretation and verify their long‑term predictive value and clinical application.