College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
Center of Children's Clinic, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
Medicine (Baltimore). 2024 Jul 26;103(30):e38957. doi: 10.1097/MD.0000000000038957.
Childhood asthma is a chronic inflammatory disease of the airways, the pathogenesis of which involves multiple factors including genetic predisposition, environmental exposure, and immune system regulation. To date, the causal relationships between immune cells, plasma metabolites, and childhood asthma remain undetermined. Therefore, we aim to utilize the Mendelian randomization approach to assess the causal relationships among immune cells, plasma metabolites, and childhood asthma. This study employed the Mendelian randomization approach to investigate how immune cells influenced the risk of childhood asthma by modulating the levels of plasma metabolites. Five Mendelian randomization methods-inverse variance weighted, weighted median, Mendelian randomization-Egger, simple mode, and weighted mode-were utilized to explore the causal relationships among 731 types of immune cells, 1400 plasma metabolites, and childhood asthma. The instrumental variables for the 731 immune cells and 1400 plasma metabolites were derived from a genome-wide association study meta-analysis. Additionally, sensitivity analyses were conducted to examine the robustness of the results, potential heterogeneity, and pleiotropy. The inverse variance weighted results indicated that HLA DR on dendritic cells (DC) is a risk factor for childhood asthma (OR: 1.08, 95% CI: 1.02-1.14). In contrast, HLA DR on DC acts as a protective factor against elevated catechol glucuronide levels (OR: 0.94, 95% CI: 0.91-0.98), while catechol glucuronide levels themselves serve as a protective factor for childhood asthma (OR: 0.73, 95% CI: 0.60-0.89). Thus, HLA DR on DC can exert a detrimental effect on childhood asthma through the negative regulation of catechol glucuronide levels. The mediating effect was 0.018, accounting for a mediation effect proportion of 23.4%. This study found that HLA DR on DC can exert a risk effect on childhood asthma through the negative regulation of catechol glucuronide levels, providing new strategies for the prevention and treatment of childhood asthma and guiding future research and clinical practice.
儿童哮喘是一种气道慢性炎症性疾病，其发病机制涉及多个因素，包括遗传易感性、环境暴露和免疫系统调节。迄今为止，免疫细胞、血浆代谢物与儿童哮喘之间的因果关系仍未确定。因此，我们旨在利用孟德尔随机化方法评估免疫细胞、血浆代谢物与儿童哮喘之间的因果关系。本研究采用孟德尔随机化方法，通过调节血浆代谢物水平，研究免疫细胞如何影响儿童哮喘的风险。我们使用了五种孟德尔随机化方法——逆方差加权、加权中位数、孟德尔随机化-Egger、简单模式和加权模式，来探讨 731 种免疫细胞、1400 种血浆代谢物与儿童哮喘之间的因果关系。731 种免疫细胞和 1400 种血浆代谢物的工具变量来源于全基因组关联研究荟萃分析。此外，还进行了敏感性分析，以检查结果的稳健性、潜在异质性和多效性。逆方差加权结果表明，树突状细胞（DC）上的 HLA-DR 是儿童哮喘的一个危险因素（OR：1.08，95%CI：1.02-1.14）。相反，DC 上的 HLA-DR 对升高的儿茶酚葡萄糖醛酸水平起保护作用（OR：0.94，95%CI：0.91-0.98），而儿茶酚葡萄糖醛酸水平本身对儿童哮喘起保护作用（OR：0.73，95%CI：0.60-0.89）。因此，DC 上的 HLA-DR 通过负向调节儿茶酚葡萄糖醛酸水平对儿童哮喘产生有害影响。中介效应为 0.018，占中介效应比例的 23.4%。本研究发现，DC 上的 HLA-DR 通过负向调节儿茶酚葡萄糖醛酸水平对儿童哮喘产生风险作用，为儿童哮喘的预防和治疗提供了新策略，并指导未来的研究和临床实践。
