解码免疫细胞与三种慢性呼吸道疾病之间的因果关联：双向孟德尔随机化研究的见解

Decoding the causal association between immune cells and three chronic respiratory diseases: Insights from a bi-directional Mendelian randomization study.

作者信息

Xie Anqi, He Zhao, Song Chenghu, Wang Ruixin, Wu Lei, Chen Ruo, Jiang Guanyu, Liu Weici, Liu Jiwei, Mao Wenjun

机构信息

Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299 Qingyang Rd., Wuxi , Jiangsu, 214023, China.

出版信息

BMC Pulm Med. 2025 Apr 15;25(1):183. doi: 10.1186/s12890-025-03641-w.

DOI:10.1186/s12890-025-03641-w

PMID:40234829

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11998255/

Abstract

BACKGROUND

Numerous studies have indicated the correlations of immune traits and chronic respiratory diseases (CRDs). Whereas, causality is still implicative. Hence, our study was designed to investigate the causal relations utilizing bidirectional Mendelian randomization (MR) and to identify the immune traits of potential significance.

METHODS

Using GWAS datasets, we performed Mendelian randomization (MR) analyses to examine 731 immune traits associated with three CRDs: asthma, bronchiectasis and chronic obstructive pulmonary disease (COPD). Six widely applied MR approaches, along with Bayesian weighted Mendelian randomization analysis, were utilized to assess causality. Through extensive sensitivity assessments, heterogeneity and pleiotropy have been examined. For integrity, leave-one-out analysis was implemented as the final step.

RESULTS

Our study reveals 13 immune traits that may have a genetic basis for predicting the occurrence of CRDs, which include two risk traits (CD62L myeloid dendritic cell (DC) absolute count (AC), CD8 on CD28 CD45RA CD8 T cell) and four protective traits (CD39 CD8 %T cell, CD4 on CD39 activated CD4 regulatory T (Treg) cell, herpes virus entry mediator (HVEM) on Central Memory (CM) CD8 T cell, CD16 on CD14 CD16 monocyte) in COPD, three protective traits (IgD CD27 %B cell, CD3 on CM CD8 T cell, CD16 on CD14 CD16 monocyte) and one risk trait (CD62L %DC) in bronchiectasis. Additionally, two risk traits (CD14 CD16 AC monocyte, CD19 on IgD CD38 B cell) and one protective trait (HVEM on CD45RA CD4 T cell) were identified in asthma. Sensitivity analyses showed no indications of pleiotropy or signs of heterogeneity. The inverse MR assessment results gave no evidence of reverse causations, ultimately validating the soundness of the findings.

CONCLUSIONS

Our investigation identifies latent correlations of immune traits and three major CRDs, offering novel perspectives on the preventive and therapeutical strategies for CRDs.

摘要

背景

众多研究表明免疫特征与慢性呼吸道疾病（CRD）之间存在关联。然而，因果关系仍不明确。因此，我们的研究旨在利用双向孟德尔随机化（MR）来研究因果关系，并确定具有潜在重要性的免疫特征。

方法

利用全基因组关联研究（GWAS）数据集，我们进行了孟德尔随机化（MR）分析，以研究与三种CRD相关的731种免疫特征：哮喘、支气管扩张和慢性阻塞性肺疾病（COPD）。采用六种广泛应用的MR方法以及贝叶斯加权孟德尔随机化分析来评估因果关系。通过广泛的敏感性评估，对异质性和多效性进行了检验。为确保完整性，最后一步进行了留一法分析。

结果

我们的研究揭示了13种可能具有预测CRD发生遗传基础的免疫特征，其中包括COPD中的两种风险特征（CD62L髓样树突状细胞（DC）绝对计数（AC）、CD28 CD45RA CD8 T细胞上的CD8）和四种保护特征（CD39 CD8 %T细胞、CD39活化的CD4调节性T（Treg）细胞上的CD4、中央记忆（CM）CD8 T细胞上的疱疹病毒进入介质（HVEM）、CD14 CD16单核细胞上的CD16），支气管扩张中的三种保护特征（IgD CD27 %B细胞、CM CD8 T细胞上的CD3、CD14 CD16单核细胞上的CD16）和一种风险特征（CD62L %DC）。此外，哮喘中还确定了两种风险特征（CD14 CD16 AC单核细胞、IgD CD38 B细胞上的CD19）和一种保护特征（CD45RA CD4 T细胞上的HVEM）。敏感性分析未显示多效性迹象或异质性迹象。反向MR评估结果未提供反向因果关系的证据，最终验证了研究结果的可靠性。