Causal Link and Shared Biomarkers Between Rheumatoid Arthritis and Idiopathic Pulmonary Fibrosis

ABSTRACT This study investigates the causal relationship between rheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF), aiming to identify shared biomarkers between the two conditions. Utilizing bidirectional Mendelian randomization (MR), we assessed causality by analyzing genome‐wide association study (GWAS) data from European cohorts, which included 14,361 RA cases and 42,923 controls, as well as 1028 IPF cases and 196,986 controls. In addition, we examined transcriptomic and single‐cell RNA sequencing (scRNA‐seq) data derived from RA patients to pinpoint shared genetic features. The MR analysis confirmed that RA is a causal factor for IPF, yielding an odds ratio of 1.156 (95% CI: 1.054‐1.267, p = 0.002), whereas no evidence supported the reverse causation. Notably, CCL2 and CXCL2 were identified as key biomarkers, displaying elevated expression levels in RA plasma ( p < 0.05) and specific immune cell types, particularly macrophages. These findings indicate that RA significantly contributes to the development of IPF and highlight CCL2 and CXCL2 as potential diagnostic markers. This research provides valuable insights that may facilitate early detection and intervention strategies for patients at risk of developing IPF in the context of RA.