Gong Peng, Lu Yimin, Chai Xi, Li Xiaobo
School of Basic Medical Sciences, Shanxi University of Traditional Chinese Medicine, Jinzhong, Shanxi, China.
Shouyang County People's Hospital, Shouyang, Shanxi, China.
J Clin Lab Anal. 2025 Apr;39(8):e70026. doi: 10.1002/jcla.70026. Epub 2025 Apr 1.
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with a complex pathogenesis involving multiple immune cells. This study investigates the relationship between immune cells and IPF using Mendelian randomization (MR) analysis.
A two-sample MR analysis was performed using genome-wide association studies (GWAS) and immune cell databases by R software. We analyzed data from 1028 European individuals with IPF, focusing on 731 immune traits. The primary method of analysis was inverse variance weighting (IVW), supplemented with sensitivity analyses, including MR-Egger regression and MR-PRESSO, to detect and correct for pleiotropy.
The MR analysis identified six immune panels and 23 immune traits significantly associated with IPF, including five traits that increase and 18 traits that decrease IPF risk. Notable traits increasing IPF risk included switched memory B-cells (OR = 1.27, p = 0.0029) and IgD- CD38dim B-cells (OR = 1.08, p = 0.0449). Traits associated with a reduced IPF risk included central memory CD4+ T-cells (%CD4+, OR = 0.96, p = 0.0489), CD20 on naive-mature B-cells (OR = 0.94, p = 0.0499), and CD33br HLA-DR+ absolute count (AC) (OR = 0.93, p = 0.0489). There was no significant causal relationship between IPF disease and some immune traits (p > 0.05).
This study suggests a potential causal link between specific immune cell traits and the development of IPF, providing new insights into the disease's immunological mechanisms. Future research should focus on validating these findings in larger, more diverse populations to inform drug development and therapeutic strategies.
特发性肺纤维化（IPF）是一种进行性且不可逆的间质性肺病，其发病机制复杂，涉及多种免疫细胞。本研究采用孟德尔随机化（MR）分析探究免疫细胞与IPF之间的关系。
使用R软件通过全基因组关联研究（GWAS）和免疫细胞数据库进行两样本MR分析。我们分析了1028名欧洲IPF患者的数据，重点关注731个免疫特征。主要分析方法为逆方差加权（IVW），并辅以敏感性分析，包括MR-Egger回归和MR-PRESSO，以检测和校正多效性。
MR分析确定了六个免疫组和23个与IPF显著相关的免疫特征，其中包括五个增加IPF风险的特征和18个降低IPF风险的特征。增加IPF风险的显著特征包括转换记忆B细胞（OR = 1.27，p = 0.0029）和IgD-CD38dim B细胞（OR = 1.08，p = 0.0449）。与降低IPF风险相关的特征包括中央记忆CD4+ T细胞（%CD4+，OR = 0.96，p = 0.0489）、幼稚-成熟B细胞上的CD20（OR = 0.94，p = 0.0499）以及CD33br HLA-DR+绝对计数（AC）（OR = 0.93，p = 0.0489）。IPF疾病与某些免疫特征之间无显著因果关系（p>0.05）。
本研究表明特定免疫细胞特征与IPF发生之间存在潜在因果联系，为该疾病的免疫机制提供了新见解。未来研究应聚焦于在更大、更多样化人群中验证这些发现，以为药物研发和治疗策略提供依据。
