支气管肺炎患儿Th2/Th17免疫失衡与气道高反应性的交互作用:基于病程-病情协同效应的风险模型

Interaction of Th2/Th17 immune imbalance and airway hyperresponsiveness in children with bronchopneumonia: a risk model based on synergistic effect of disease course and severity

  • 摘要:
    目的 探讨支气管肺炎患儿辅助性T细胞亚群分布特征并分析辅助性T细胞亚群与气道高反应性(AHR)的相关性。
    方法 选择甘肃医学院附属医院2019年9月-2024年6月收治的183例支气管肺炎患儿作为研究对象,另选63例同期健康儿童作为对照组,对比支气管肺炎患儿和健康儿童辅助性T细胞亚群分布。根据气道反应性检测将支气管肺炎患儿分为AHR组(n=61)和无气道高反应性(NAHR)组(n=67),对比两组患儿临床资料及辅助性T细胞亚群分布,筛选支气管肺炎患儿AHR的危险因素,建立模型并比较模型预测效能,分析危险因素对气道反应性影响的交互作用,并对辅助性T细胞亚群与支气管肺炎患儿气道高反应的关联性进行分析。
    结果 重症组患儿辅助性T淋巴细胞(Th)1、白细胞介素-2(IL-2)及干扰素γ(IFN-γ)水平分别为(8.72±1.81)%、(6.62±1.22)μg/L及(7.32±1.74)mg/L,低于轻症组和对照组,且Th2、IL-10、IL-17及转化生长因子-β(TGF-β)水平分别为(12.06±3.12)%、(23.28±5.68)、(46.53±6.69)及(36.24±6.45)ng/L,高于轻症组及对照组(P<0.05),轻症组患儿Th17、IL-10、IL-17及TGF-β水平高于对照组,IL-2和IFN-γ水平低于对照组(P<0.05);病程(OR=1.536)、病情程度(OR=3.267)、Th2(OR=2.274)及Th17水平(OR=1.772)是支气管肺炎患儿AHR的危险因素(P<0.05),基于以上4个因素构建的模型C指数高于其他模型;调整混杂因素后,Th2和Th17水平仍为支气管肺炎患儿AHR的危险因素,随着Th2、Th17水平的升高,其关联效应值也相应升高(P趋势<0.001);支气管肺炎病情程度与Th2水平在相加模型中存在交互作用,支气管肺炎病情程度与Th17水平在相乘、相加模型中均存在交互作用,表现为协同作用。
    结论 支气管肺炎患儿Th2/Th17免疫失衡与疾病程度及气道高反应性密切相关,二者存在交互作用。调控Th2/Th17通路可能成为改善支气管肺炎气道炎症的新方向。

     

    Abstract:
    OBJECTIVE  To explore the distribution characteristics of helper T cell subsets in children with bronchopneumonia and analyze the correlation between helper T cell subsets and airway hyperresponsiveness (AHR).
    METHODS  A total of 183 children with bronchopneumonia admitted to the Affiliated Hospital of Gansu Medical College from Sep. 2019 to Jun. 2024 were selected as the study subjects, and another 63 healthy children during the same period were selected as the control group to compare the distribution of helper T cell subsets between children with bronchopneumonia and healthy children. According to airway responsiveness, children with bronchopneumonia were divided into an AHR group (n=61) and a non-airway hyperresponsiveness (NAHR) group (n=67). Clinical data and the distribution of helper T cell subsets were compared between the two groups. Risk factors for AHR in children with bronchopneumonia were screened, a model was established, and its predictive performance was tested. The interactive effect of risk factors on airway responsiveness was analyzed, and the correlation between helper T cell subsets and airway hyperresponsiveness in children with bronchopneumonia was also analyzed.
    RESULTS  In the severe group, the levels of helper T lymphocyte (Th) 1, interleukin-2 (IL-2) and interferon-γ (IFN-γ) were (8.72±1.81)%, (6.62±1.22) μg/L and (7.32±1.74) mg/L, respectively, which were lower than those in the mild group and the control group. And the levels of Th2, IL-10, IL-17 and transforming growth factor-β (TGF-β) were (12.06±3.12)%, (23.28±5.68), (46.53±6.69) and (36.24±6.45) ng/L, respectively, which were higher than those in the mild group and the control group (P<0.05). In the mild group, the levels of Th17, IL-10, IL-17 and TGF-β were higher than those in the control group, while the levels of IL-2 and IFN-γ were lower than those in the control group (P<0.05). Disease course (OR=1.536), disease severity (OR=3.267), Th2 level (OR=2.274) and Th17 level (OR=1.772) were identified as risk factors for airway hyperresponsiveness (AHR) in children with bronchopneumonia (P<0.05). The C-index of the model constructed based on these four factors was higher than that of other models. After adjusting confounding factors, Th2 and Th17 levels remained risk factors for AHR in children with bronchopneumonia. As the levels of Th2 and Th17 increased, their associated effect values also increased accordingly (Ptrend<0.001). There was an interaction between the severity of bronchopneumonia and Th2 level in the additive model, and between the severity of bronchopneumonia and Th17 level in both multiplicative and additive models, all demonstrating a synergistic effect.
    CONCLUSIONS  Th2/Th17 immune imbalance in children with bronchopneumonia is closely related to disease severity and airway hyperresponsiveness, and there are interactions between them. Regulating the Th2/Th17 pathway may represent a new direction for improving airway inflammation in bronchopneumonia.

     

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