Causal Links between Immune Cells and Asthma: Insights from a Mendelian Randomization Analysis

Recent studies suggest immunophenotypes may play a role in asthma, but their causal relationship has not been thoroughly examined. We used single nucleotide polymorphism (SNP)-derived instrumental variables. Summary data from 731 immune cell profiles and asthma cases were analyzed from genome-wide association studies (GWAS) of European populations. Mendelian Randomization (MR) analyses included inverse variance weighted (IVW), weighted median, and MR–Egger methods. Pleiotropy was assessed using the MR-Egger intercept and MR pleiotropy residual sum and outlier (MR-PRESSO) tests. Reverse MR analysis explored bidirectional causation between asthma and immunophenotypes. All statistical analyses were conducted using R software. MR analysis identified 108 immune signatures potentially contributing to asthma. Two immunophenotypes were significantly associated with asthma risk: CD4+ secreting Treg cells in allergic asthma (OR_IVW =1.078; 95% CI: 1.036–1.122; P_IVW =0.0002) and IgD + CD38- %lymphocyte cells in non-allergic asthma (OR_IVW =1.123; 95% CI: 1.057–1.194; P_IVW =0.0002). This study highlights the causal associations between specific immunophenotypes and asthma risk, providing new insights into asthma pathogenesis.

近期研究表明免疫表型可能在哮喘发病过程中发挥作用，但其与哮喘的因果关联尚未得到充分探究。本研究采用基于单核苷酸多态性（single nucleotide polymorphism, SNP）的工具变量，对欧洲人群全基因组关联研究（genome-wide association studies, GWAS）中731份免疫细胞谱与哮喘病例的汇总数据进行分析。孟德尔随机化（Mendelian Randomization, MR）分析涵盖逆方差加权（inverse variance weighted, IVW）、加权中位数法及MR-Egger法三种分析策略；多效性通过MR-Egger截距项与MR多效性残差和异常值（MR pleiotropy residual sum and outlier, MR-PRESSO）检验进行评估。反向MR分析探究了哮喘与免疫表型间的双向因果关系，所有统计分析均通过R软件完成。

MR分析共筛选出108个可能与哮喘发病相关的免疫特征。其中两种免疫表型与哮喘风险存在显著关联：过敏性哮喘患者体内的分泌型CD4+调节性T细胞（IVW法OR=1.078；95%CI：1.036–1.122；IVW法P=0.0002），以及非过敏性哮喘患者体内的IgD+CD38-淋巴细胞占比（IVW法OR=1.123；95%CI：1.057–1.194；IVW法P=0.0002）。本研究揭示了特定免疫表型与哮喘风险间的因果关联，为哮喘发病机制的研究提供了全新视角。