The potential pathogenic mechanism of idiopathic pulmonary fibrosis is widely recognized to involve immune dysregulation. However, the current pool of studies has yet to establish a unanimous agreement regarding the correlation between various types of immune cells and IPF. By conducting a two-sample Mendelian randomization analysis using publicly available genetic data, the study examined the causal relationship between IPF and 731 immune cells. To ensure the reliability of the results, combined sensitivity analyses and inverse Mendelian analyses were conducted. Moreover, within subgroups, multivariate Mendelian randomization analyses were utilized to investigate the autonomous causal connection between immune cell characteristics and IPF. After adjusting for false discovery rate, it was discovered that 20 immunophenotypes exhibited a significant association with IPF. After subgrouping for multivariate Mendelian randomization analysis, there were six immunophenotypes that remained significantly associated with IPF. These included CD33 + HLA DR + CD14dim (OR = 0.96, 95% CI 0.93–0.99, P = 0.033), HLA DR + NK (OR = 0.92, 95% CI 0.85–0.98, P = 0.017), CD39 + CD8 + T cell %T cell (OR = 0.93, 95% CI 0.88–0.99, P = 0.024), CD3 on activated & secreting Treg (OR = 0.91, 95% CI 0.84–0.98, P = 0.026), PDL-1 on CD14- CD16 + monocyte (OR = 0.89, 95% CI 0.84–0.95, P = 8 × 10–4), and CD45 on CD33 + HLA DR + CD14- (OR = 1.08, 95% CI 1.01–1.15, P = 0.011). Our study reveals a noteworthy association between IPF and various immune cells, providing valuable insights for clinical research and aiding the advancement of immunologically-based therapeutic strategies.

中文翻译：

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探索免疫细胞与特发性肺纤维化之间的因果关系：双向孟德尔随机化研究

特发性肺纤维化的潜在致病机制被广泛认为涉及免疫失调。然而，目前的研究尚未就各类免疫细胞与 IPF 之间的相关性达成一致。通过使用公开的遗传数据进行两个样本孟德尔随机化分析，该研究检查了 IPF 和 731 种免疫细胞之间的因果关系。为了确保结果的可靠性，结合敏感性分析和逆孟德尔分析。此外，在亚组内，利用多变量孟德尔随机化分析来研究免疫细胞特征与 IPF 之间的自主因果关系。在调整错误发现率后，发现 20 种免疫表型与 IPF 显着相关。在进行多变量孟德尔随机化分析分组后，有六种免疫表型仍然与 IPF 显着相关。其中包括 CD33 + HLA DR + CD14dim（OR = 0.96，95% CI 0.93–0.99，P = 0.033）、HLA DR + NK（OR = 0.92，95% CI 0.85–0.98，P = 0.017）、CD39 + CD8 + T 细胞 %T 细胞（OR = 0.93，95% CI 0.88–0.99，P = 0.024），激活和分泌 Treg 上的 CD3（OR = 0.91，95% CI 0.84–0.98，P = 0.026），CD14 上的 PDL-1 - CD16 + 单核细胞（OR = 0.89，95% CI 0.84–0.95，P = 8 × 10–4），以及 CD33 + HLA DR + CD14- 上的 CD45（OR = 1.08，95% CI 1.01–1.15，P = 0.011 ）。我们的研究揭示了 IPF 与各种免疫细胞之间的显着关联，为临床研究提供了宝贵的见解，并有助于推进基于免疫学的治疗策略。