RELATIONSHIP BETWEEN MEMBRANE-BOUND AND SOLUBLE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS AND DISEASE ACTIVITY IN JUVENILE IDIOPATHIC ARTHRITIS PATIENTS

Background: Membrane-bound receptor for advanced glycation endproducts (mRAGE) expression increases in the presence of its ligands (e.g., High Mobility Group Box 1, HMGB1) and triggers an inflammatory immune response. In contrast, soluble RAGE (sRAGE) acts as a decoy receptor and downmodulates inflammation. Some studies have demonstrated that decreased sRAGE levels are negatively correlated with disease activity in juvenile idiopathic arthritis (JIA) but expression of mRAGE has not been studied. Objectives: The aim of this study is to evaluate mRAGE and sRAGE on peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MC) of patients with JIA and healthy controls and to assess whether there is an association with established inflammatory markers and clinical measures. Methods: Matching samples of blood and synovial fluid were collected from patients with JIA (n=33) with active arthritis. RAGE expression on mononuclear cells was analyzed using flow cytometry. The intensity of RAGE expression was measured as mean fluorescence intensity (MFI). Levels of sRAGE and HMGB1 were determined with a specific ELISA kit in the serum and synovial fluid (SF) of patients with JIA. Relation between cellular RAGE and sRAGE with disease activity parameters [JADAS71, CHAQ, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] and HMGB1 were described. We compare mRAGE expression in PBMC and serum sRAGE levels between JIA patients and age-matched healthy controls (n=43). Results: 24 patients with oligoarticular JIA and 9 patients with poliarticular JIA were studied, 8/23 females with a mean age of 7,7 ± 3,6. MFI of mRAGE in PBMC and SFMC of JIA patients were significantly decreased in comparison with MFI of mRAGE in PBMC of healthy controls. Although serum levels of sRAGE were not different between patients and controls, sRAGE levels were lower in SF (570.2 [458.5- 773.0]) compared to PB (759.7 [628.6-890.3]) in JIA patients, especially in the poliarticular group. By contrast, HMGB1 levels in SF were significantly higher than in PB of JIA patients. MFI of mRAGE in PBMC was correlated with JADAS71 (p 0.01) and CHAQ (p 0.07). There were no significant correlations between serum sRAGE and HMGB1 with JADAS71, CHAQ, CRP and ESR. Conclusion: The sRAGE/RAGE system may be a modulator of inflammation in JIA patients. Differences between levels of sRAGE and HMGB1 in synovial fluid versus peripheral blood in patients with JIA may suggest a local role in the pathogenesis of JIA. Disclosure of Interests: Daniel Clemente Paid instructor for: Novartis, Speakers bureau: Novartis, Abvie, Roche, Sobi, Alberto Garcia-Salido: None declared, Gustavo Melen: None declared, Manuel Ramirez-Orellana: None declared, J.C. Lopez Robledillo: None declared