Exploring the Causal Relationship Between Immune Cells and Idiopathic Pulmonary Fibrosis: A Mendelian Randomization Analysis.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.