Exploring the impact of cuproptosis-related genes on immune infiltration in rheumatoid arthritis.

Immune infiltration plays a significant role in the pathogenesis of rheumatoid arthritis (RA). Cuproptosis, a newly characterized form of programmed cell death, remains insufficiently investigated regarding its genetic regulation of immune infiltration in RA. Data from the GEO database were analyzed to determine the relationship between cuproptosis-related genes and immune infiltration. Comprehensive analyses, including Gene Ontology, and KEGG pathway enrichment were performed to construct a risk model and provide a theoretical framework for understanding the mechanisms underlying the involvement of cuproptosis in RA-related immune infiltration. And we explored the expression of related genes-PDHB in animal and cell experiments. The findings revealed substantial variations in immune infiltration between RA and control groups. Eleven cuproptosis-related genes associated with RA were identified, namely DLST, LIAS, DLAT, DLD, PDHB, Lipt1, DBT, ATP7B, SLC31A1, FDX1, and PDHA1. Among these, DLST and PDHB emerged as potential risk factors influencing RA pathogenesis. These genes modulated immune cell alterations, including changes in iDCs, NK-cells, mast cells, and pDCs, alongside impacts on immune functions specific to RA. In animal experiments, we found that the expression of PDHB is decreased; overexpression of PDHB by PDHB gene transfection inhibited the migration, invasion, and proliferation of FLS cells.