Disulfidptosis- and Ferroptosis-Related Gene Signatures in Rheumatoid Arthritis: Association Analysis and Diagnostic Model Construction.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint damage. Although ferroptosis has been implicated in RA progression, the role of disulfidptosis and its interaction with ferroptosis remains unclear. This study aimed to identify Disulfidptosis- and Ferroptosis-Related Genes (DFRGs) associated with RA and construct a candidate diagnostic model. Blood transcriptomic data from 154 RA patients and 43 healthy controls were analyzed. Differentially expressed DFRGs were identified, and immune infiltration was assessed using single-sample Gene Set Enrichment Analysis (ssGSEA). Feature genes were selected through correlation analysis and logistic regression, followed by construction of a diagnostic nomogram. External validation was performed using independent datasets. Potential regulatory miRNAs and therapeutic agents were predicted, and single-cell eQTL-based Mendelian randomization (MR) was used to evaluate genetic associations between core gene expression and RA risk. Eleven DFRGs were identified and were enriched in p53, mTOR, and immune-related pathways. Five feature genes, DUOX1, DRD4, ATP6V1G2, ASNS, and CDKN1A, were used to establish a diagnostic model with favorable performance in the training cohort and external validation datasets. Five key miRNAs and 61 potential therapeutic agents were predicted. MR suggested that ASNS expression may be protective, whereas ATP6V1G2 expression may increase RA risk. These findings suggest that DFRGs-related signatures may be involved in RA pathogenesis and immune dysregulation, although further in vitro and in vivo validation is required.