Session Type: Abstract Submissions (ACR)
Background/Purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and subsequent joint damage with systemic manifestations. Interleukin-20 (IL-20) has been previously identified as a pro-inflammatory cytokine that may be implicated in the pathogenesis of chronic inflammatory diseases, particularly RA (1). Recently, phase 2a trial (2) demonstrated that treatment with anti-IL-20 monoclonal antibody significantly reduced disease activity in seropositive patients with RA. Therefore, the aim of the current study was to characterize the role of IL-20 in patients with RA.
Methods: The levels of serum and synovial fluid IL-20 were measured by ELISA assay in 34 patients with RA (25 female) and 35 patients with OA (19 female). Disease activity was assessed based on the Disease Activity Score of 28 joints (DAS28). The expression of IL-20 in synovial tissue samples from patients with RA (n=5) and OA (n=7) were determined by immunohistochemistry. Secretion of IL-20 was analysed in human peripheral blood mononuclear cells (PBMCs) isolated from blood of patients with RA (n=8).
Results: The expression of IL-20 was significantly up-regulated in RA compared with OA synovial tissue, particularly in the lining (2.6±0.65 vs 0.93±0.19; p=0.003) as well as in the inflammatory infiltrates of the sublining layer (2.2±0.57 vs 0.37±0.36; p=0.005). The levels of IL-20 in synovial fluid were significantly higher in patients with RA compared to those with OA (86.3±87.5 vs 41.9±43.3 pg/ml; p=0.01). IL-20 production from PBMCs was induced by Poly I:C (TLR-3 ligand) (p<0.0001) and LPS (TLR-4 ligand) (p=0.0008), but not with pro-inflammatory cytokines such as TNFα (p=0.99) or IL-1 (p=0.74).
In contrast to local sites of inflammation, serum levels of IL-20 in RA patients were comparable to those in OA patients (41.7 ± 48.7 vs 32.3 ± 45.4 pg/ml; p=NS), and significantly correlated with DAS28 (r=0.581; p=0.001) and anti-CCP levels (r=0.362; p=0.045). When adjusted for anti-CCP levels, correlation with DAS28 remained still significant (r=0.540; p=0.002). Similarly, the levels of IL-20 in synovial fluid correlated with RA disease activity. In addition, the levels of IL-20 in synovial fluid were significantly higher in anti-CCP positive compared to anti-CCP negative patients with RA (122.3±104.1 and 45.9±35.8 pg/ml; p=0.008); this difference was however not paralleled by serum IL-20 levels (51±48.6 and 31.1±48.2 pg/ml; p=0.24).
Conclusion: Our data show that IL-20 is independently associated with RA disease activity and may be triggered by TLR ligands at local sites of inflammation. Association between IL-20 and anti-CCP levels may, at least partially, explain disease activity improvement after the treatment with anti-IL-20 monoclonal antibody in seropositive RA patients.
Hsu YH, et al. Arthritis Rheum. 2006;54:2722-33.
Šenolt L, et al. Arthritis Rheum. 2012;64(suppl 10):S364.
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