Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Medicine (Baltimore). 2024 Sep 13;103(37):e39670. doi: 10.1097/MD.0000000000039670.
Immunity and inflammation in pulmonary arterial hypertension (PAH) has gained more attention. This research aimed to investigate the potential causal connections between 731 immunophenotypes and the likelihood of developing PAH. We obtained immunocyte data and PAH from openly accessible database and used Mendelian randomization (MR) analysis to evaluate the causal association between each immunophenotype and PAH. Various statistical methods were employed: the MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode. In the study of 731 different types of immune cells, it was found that 9 showed a potential positive connection (IVW P < .05) with increased risk of PAH, while 19 had a possible negative link to decreased risk. Following false discovery rate (FDR) adjustment, the analysis using the IVW method demonstrated that 5 immune phenotypes were significantly associated with PAH (FDR < 0.05, OR > 1). Conversely, there was a negative correlation between PAH and 4 immune cell types (FDR < 0.05, OR < 1). Sensitivity analyses suggested the robustness of all MR findings. This research, for the first time, has revealed indicative evidence of a causal link between circulating immune cell phenotypes and PAH through genetic mechanisms. These results underscore the importance of immune cells in the pathogenesis of PAH.
肺动脉高压（PAH）中的免疫和炎症受到了更多的关注。本研究旨在探讨 731 种免疫表型与 PAH 发生的可能性之间潜在的因果关系。我们从公开可获得的数据库中获取免疫细胞数据和 PAH，并使用孟德尔随机化（MR）分析评估每个免疫表型与 PAH 之间的因果关联。采用了多种统计方法：MR-Egger、加权中位数、逆方差加权（IVW）、简单模式和加权模式。在对 731 种不同类型免疫细胞的研究中，发现其中 9 种与 PAH 风险增加有潜在的正相关（IVW P<0.05），而 19 种与风险降低有潜在的负相关。经过虚假发现率（FDR）调整后，IVW 方法分析表明，有 5 种免疫表型与 PAH 显著相关（FDR<0.05，OR>1）。相反，PAH 与 4 种免疫细胞类型呈负相关（FDR<0.05，OR<1）。敏感性分析表明所有 MR 结果都具有稳健性。这项研究首次通过遗传机制揭示了循环免疫细胞表型与 PAH 之间存在因果关系的指示性证据。这些结果强调了免疫细胞在 PAH 发病机制中的重要性。
