Lactylation-related genes serve as potential markers for the diagnosis and immune infiltration in rheumatoid arthritis.

Abstract

Lactylation is widely involved in cellular processes and is pivotal in inflammation and immune regulation. However, the expression and clinical significance of lactylation in rheumatoid arthritis (RA) remain unclear. This study aimed to determine the role of lactylation in RA and its association with immune cell infiltration. We initially detected the levels of lactate in the plasma of RA patients and the levels of panlysine lactylation (Pan-Kla) in peripheral blood mononuclear cells (PBMCs). Next, we used differential expression analysis and weighted gene coexpression network analysis (WGCNA) to intersect with lactylation-related genes. We obtained lactylation-related differentially expressed genes (LADEGs) in RA and analyzed their functional enrichment. We subsequently used the CIBERSORT algorithm to analyze immune cell infiltration in RA synovial tissues and its correlation with LADEGs. Finally, key genes of LADEGs were validated in the Pathobiology of Early Arthritis Cohort (PEAC) study and our samples. Our study revealed elevated levels of lactate and lactylation in the peripheral blood of RA patients. IKAROS family zinc finger 1 (IKZF1), lymphocyte cytosolic protein 1 (LCP1), and WASP actin-nucleation promoting factor (WAS) may be potential biomarkers for early diagnosis and assessment of disease activity in RA.