Causal effect of immune cells on idiopathic pulmonary fibrosis: A mendelian randomization study

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⁺ CD8⁺T cells (odd ratio [OR] = 0.850, 95 % confidence interval [CI] = 0.787-0.918, P = 3.68 × 10^-5). 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⁺ CD8⁺T cells showed a protective effect against IPF, providing effective insights for preventing and diagnosing pulmonary fibrosis.