Anti-LL-37 antibodies in synovial fluid reflect disease-specific immunopathogenic mechanisms in psoriatic arthritis

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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 (KoA), and to analyze their associations with pro-inflammatory cytokines. Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by dysregulated innate and adaptive immune responses. Autoantibodies against the antimicrobial peptide LL-37 have recently emerged as potential contributors to PsA pathogenesis, although their relationship with synovial cytokine profiles and disease activity remains insufficiently characterized. To investigate synovial anti-LL-37 autoantibody levels in patients with PsA and evaluate their association with inflammatory cytokines, clinical disease activity, and laboratory markers of inflammation. A total of 120 participants were enrolled, including 30 patients with PsA, 30 with RA, 30 with KoA, and 30 non-inflammatory orthopedic controls. Synovial fluid concentrations of anti-LL-37 antibodies, IL-1β, IL-6, and IL-23 were measured. Clinical and laboratory parameters, including CRP, ESR, BMI, and disease activity scores (DAPSA for PsA and DAS28 for RA), were recorded. Group differences were analyzed using appropriate comparative statistics, followed by post hoc testing. Spearman correlation and multiple linear regression analyses were performed to identify associations and independent predictors of anti-LL-37 levels. Patients with PsA demonstrated significantly higher synovial anti-LL-37 antibody concentrations than patients with RA, KoA, and controls (all p = 0.001). IL-23 levels were also significantly elevated in PsA, whereas IL-1β and IL-6 were highest in RA. In PsA, anti-LL-37 levels showed strong positive correlations with IL-23 (ρ = 0.962, p < 0.001), IL-1β (ρ = 0.855, p < 0.001), IL-6 (ρ = 0.627, p < 0.001), DAPSA score (ρ = 0.874, p < 0.001), and CRP (ρ = 0.618, p = 0.001). Similar but weaker correlations were observed in RA, while no significant associations were identified in KoA or controls. Multiple linear regression analysis demonstrated that DAPSA score was the only independent predictor of synovial anti-LL-37 antibody levels (β = 0.384, p = 0.026). The regression model explained 89.1% of the variance in anti-LL-37 concentrations (adjusted R2 = 0.891). Synovial anti-LL-37 autoantibodies are markedly increased in PsA and are closely associated with IL-23-driven inflammation and clinical disease activity. These findings support the involvement of LL-37-directed autoimmunity in PsA pathogenesis and suggest that synovial anti-LL-37 antibodies may represent a promising synovial biomarker for disease activity and a potential therapeutic target in psoriatic arthritis.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.