Examining the Involvement of Ferroptosis-Related Genes in Ankylosing Spondylitis and the Infiltration of Immune Cells

Ankylosing Spondylitis (AS) is a chronic inflammatory disease which is characterized by pain and progressive stiffness and which spinal and sacroiliac joints are mainly affected, with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a regulated form of cell death that is important for normal development and tissue homeostasis. However, its relation to AS is not clear. In this study, we identified two potential therapeutic targets for AS based on genes associated with ferroptosis and explored their association with immune cell infiltration (ICI) and immune cells. We studied gene expression profiles of two cohorts of patients with AS (GSE73754 and GSE41038) derived from the gene expression omnibus database at NCBI, and ferroptosis-associated genes (FRGs) were obtained from the FerrDb database. LASSO regression analysis was performed to estimate predictive factors for AS based on FRGs, and the ferroptosis level in each sample was performed via single-sample gene set enrichment analysis. Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analyses were assessed. The relationship between key genes and ICI levels was assessed using the CIBERSORT algorithm, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. These results suggest that ALKBH5 and NDUFA12 might serve as potential diagnostic biomarkers and targets for AS. And both was negatively correlated with the infiltration levels of several different types of immune cells. In conclusion, ALKBH5 and NDUFA12 may induce ferroptosis in the cells of patients with AS via changes in the inflammatory response in the immune microenvironment, and these genes could serve as molecular targets for AS therapy.