“Synovial Anti-LL-37 Antibodies Are Associated with IL-23–Driven Immune Activation in Psoriatic Arthritis”—Cross-Sectional Exploratory Study

Background: The antimicrobial peptide LL-37 has emerged as a key mediator linking innate and adaptive immunity and has been implicated in the pathogenesis of immune-mediated inflammatory diseases. While circulating levels of LL-37 and anti-LL-37 antibodies have been investigated in several conditions, their presence and relevance within the local joint microenvironment remain insufficiently explored. This study aimed to evaluate anti-LL-37 antibodies in synovial fluid from patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and knee osteoarthritis (GoA), and to analyze their associations with pro-inflammatory cytokines. Methods: Synovial fluid samples were obtained from patients with PsA, RA, GoA, and from healthy controls. Levels of anti-LL-37 antibodies, IL-1β, IL-6, and IL-23 were measured using enzyme-linked immunosorbent assay (ELISA). Correlation analyses were performed to assess relationships between anti-LL-37 antibodies and cytokine levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of anti-LL-37 antibodies. Results: Anti-LL-37 antibody levels were significantly elevated in synovial fluid from patients with PsA compared to RA, GoA, and healthy controls. Patients with RA exhibited lower anti-LL-37 levels despite pronounced elevations of IL-1β and IL-6. In GoA, anti-LL-37 concentrations were comparable to those of healthy controls. A strong positive correlation between anti-LL-37 antibodies and IL-23 was observed in PsA, whereas correlations with IL-1β and IL-6 were more prominent in RA. ROC analysis demonstrated moderate diagnostic accuracy of anti-LL-37 antibodies in distinguishing PsA from healthy controls, but limited utility in RA and GoA. Conclusions: The findings support a disease-specific role of anti-LL-37 antibodies in the immunopathogenesis of psoriatic arthritis and highlight their association with the IL-23/Th17 axis within the synovial microenvironment. Anti-LL-37 antibodies may serve as a complementary biomarker for PsA and provide further insight into the distinct immunological mechanisms underlying inflammatory versus degenerative joint diseases.