Department of Otolaryngology, Head and Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Rapid Diagnosis and Precision Treatment of Airway Allergic Diseases, Head & Neck Surgery, Second Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
Front Immunol. 2024 May 15;15:1349470. doi: 10.3389/fimmu.2024.1349470. eCollection 2024.
Airway allergic disease (AAD) is a class of autoimmune diseases with predominantly Th2-type inflammation, mainly including allergic rhinitis (AR), allergic asthma (AS), and chronic sinusitis (CRS). There are very complex regulatory mechanisms between immune cells and AAD; however, previous reports found that the functions of the same immune cells in AAD are not identical.
The aim of this study was to explore the causal relationship between different phenotypic immune cells and their association with AAD.
Utilizing the publicly available Genome-Wide Association Studies (GWAS) database, this study conducted a bidirectional Mendelian randomization (MR) to assess the causal relationship between immune cells of 731 different immunophenotypes and AAD. The primary assessment methods included inverse variance weighting, weighted median, and MR Egger. Additionally, sensitivity analyses such as MR-PRESSO, leave-one-out, and scatter plots were employed to eliminate the interference of heterogeneity and pleiotropy, ensuring the stability of the causal inference.
A total of 38 immune cells with different immunophenotypes were found to be positively and causally associated with AR, of which 26 were protective factors and 12 were risk factors. Positive associations were found between 33 immune cells and AS, of which 14 were protective factors and 19 were risk factors, as well as between 39 immune cells and CRS, of which 22 were protective factors and 17 were risk factors. Finally, the results of all relevant immune cells for the three diseases were taken and intersected, and it was found that CD3 on CD39+-activated Treg (IVW = 0.001, IVW = 0.043, IVW = 0.027) may be the key immune cell that inhibits the development of AAD (OR = 0.940, OR = 0.967, OR = 0.976).
This study reveals that different immune phenotypes of immune cells are closely related to AAD at the genetic level, which provides a theoretical basis for future clinical studies.
气道过敏性疾病（AAD）是一类以 Th2 型炎症为主的自身免疫性疾病，主要包括过敏性鼻炎（AR）、过敏性哮喘（AS）和慢性鼻窦炎（CRS）。免疫细胞与 AAD 之间存在非常复杂的调控机制，但以往的报道发现，同种免疫细胞在 AAD 中的功能并不相同。
本研究旨在探讨不同表型免疫细胞与 AAD 的因果关系及其相关性。
利用公开的全基因组关联研究（GWAS）数据库，本研究采用双向孟德尔随机化（MR）评估了 731 种不同免疫表型的免疫细胞与 AAD 之间的因果关系。主要评估方法包括逆方差加权、加权中位数和 MR Egger。此外，还采用了 MR-PRESSO、单样本剔除和散点图等敏感性分析方法，以消除异质性和多效性的干扰，确保因果推断的稳定性。
共发现 38 种具有不同免疫表型的免疫细胞与 AR 呈正相关且具有因果关系，其中 26 种为保护因素，12 种为风险因素。33 种免疫细胞与 AS 呈正相关，其中 14 种为保护因素，19 种为风险因素，39 种免疫细胞与 CRS 呈正相关，其中 22 种为保护因素，17 种为风险因素。最后，对三种疾病相关的所有免疫细胞结果进行取交集，发现 CD39+活化 Treg 上的 CD3（IVW=0.001，IVW=0.043，IVW=0.027）可能是抑制 AAD 发展的关键免疫细胞（OR=0.940，OR=0.967，OR=0.976）。
本研究揭示了免疫细胞的不同免疫表型在遗传水平上与 AAD 密切相关，为未来的临床研究提供了理论依据。
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