College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
The First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Heart Lung. 2024 Nov-Dec;68:9-17. doi: 10.1016/j.hrtlng.2024.06.003. Epub 2024 Jun 11.
A key component of idiopathic pulmonary fibrosis (IPF) is the involvement of immune cells. However, the causal interaction between different immune cell signatures and IPF remain inconclusive.
Based on publicly accessible data, our study utilized the Mendelian randomization (MR) approach to determine the causative relevance of complex immune cell phenotypes in IPF.
We deployed a two-sample Mendelian randomization approach to evaluate the causal interaction between immune cell markers and IPF. All data regarding 731 immune signatures and IPF were acquired from two genome-wide association studies (GWAS) that are accessible to the public. The original study adopted the inverse variance weighted (IVW) method, followed by sensitivity analyses aimed at eliminating heterogeneity and pleiotropy. Additionally, Multivariate Mendelian randomization (MVMR) was utilized to identify the independent risk factors in our study.
The summary dataset for IPF was accessed from the Finnish Genetic Consortium R9, comprising 2018 patients and 373,064 controls. And the dataset for immune signatures was conducted in 3,757 Sardinian individuals. By conducting IVW and extensive sensitivity analyses, univariate Mendelian randomization (UVMR) identified one immunophenotype that remained causally associated with IPF after false discovery rate (FDR) correction: CD39 on CD39 CD8T cells (odd ratio [OR] = 0.850, 95 % confidence interval [CI] = 0.787-0.918, P = 3.68 × 10). The causal association with IPF was further validated using MVMR.
Based on rigorous MR analysis methods and FDR correction, our study demonstrated that CD39 on CD39 CD8T cells showed a protective effect against IPF, providing effective insights for preventing and diagnosing pulmonary fibrosis.
特发性肺纤维化（IPF）的一个关键组成部分是免疫细胞的参与。然而，不同免疫细胞特征与 IPF 之间的因果相互作用仍不确定。
基于可公开获取的数据，我们的研究利用孟德尔随机化（MR）方法来确定 IPF 中复杂免疫细胞表型的因果相关性。
我们采用两样本孟德尔随机化方法来评估免疫细胞标志物与 IPF 之间的因果相互作用。所有关于 731 个免疫特征和 IPF 的数据均来自两个可公开获取的全基因组关联研究（GWAS）。原始研究采用逆方差加权（IVW）方法，随后进行敏感性分析以消除异质性和多效性。此外，还使用多变量孟德尔随机化（MVMR）来识别我们研究中的独立风险因素。
我们从芬兰遗传联盟 R9 中获取了 IPF 的汇总数据集，其中包括 2018 名患者和 373064 名对照。免疫特征数据集是在 3757 名撒丁岛个体中进行的。通过进行 IVW 和广泛的敏感性分析，单变量孟德尔随机化（UVMR）确定了一个免疫表型在经过错误发现率（FDR）校正后仍然与 IPF 具有因果关系：CD39 阳性的 CD39 CD8T 细胞（比值比[OR] = 0.850，95%置信区间[CI] = 0.787-0.918，P = 3.68×10）。使用 MVMR 进一步验证了与 IPF 的因果关系。
基于严格的 MR 分析方法和 FDR 校正，我们的研究表明 CD39 阳性的 CD39 CD8T 细胞对 IPF 具有保护作用，为预防和诊断肺纤维化提供了有效的见解。
