Multi-omics analysis reveals causal relationship and shared biomarkers between rheumatoid arthritis and pulmonary fibrosis

Rheumatoid arthritis (RA) is a common autoimmune disease, and approximately 30%-40% of patients develop pulmonary complications such as idiopathic pulmonary fibrosis (IPF), but the causal relationship between the two has long been unclear. A team from Taizhou Hospital in Zhejiang Province conducted a study using multiple omics methods, including bidirectional Mendelian randomization, transcriptomics, and single-cell RNA sequencing.

Analysis of genomic data from European populations (14,361 RA cases, 42,923 controls, 1,028 IPF cases, and 196,986 controls) revealed that RA is a causal factor for IPF (OR=1.156, P=0.002), while IPF is not a causative factor for RA. Further studies showed that CCL2 and CXCL2 were significantly upregulated in RA patients, closely associated with the inflammatory and fibrotic mechanisms of IPF. ELISA experiments confirmed that the concentrations of both were significantly elevated in the plasma of RA patients, with an area under the curve of 0.867 for combined diagnosis, demonstrating good sensitivity and specificity.

These findings not only clarify the causal relationship between RA and IPF, but also provide biomarkers that can be used for early diagnosis, laying the foundation for precise intervention.