Chen Yueh-Sheng, Yan Weixing, Geczy Carolyn L, Brown Matthew A, Thomas Ranjeny
Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Australia.
Arthritis Res Ther. 2009;11(2):R39. doi: 10.1186/ar2645. Epub 2009 Mar 11.
The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage.
Serum sRAGE, S100A9, S100A8 and S100A12 levels from 138 patients with established RA and 44 healthy controls were measured by ELISA and compared by unpaired t test. In RA patients, associations with disease activity and severity variables were analyzed by simple and multiple linear regressions.
Serum S100A9, S100A8 and S100A12 levels were correlated in RA patients. S100A9 levels were associated with body mass index (BMI), and with serum levels of S100A8 and S100A12. S100A8 levels were associated with serum levels of S100A9, presence of anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF). S100A12 levels were associated with presence of ACPA, history of diabetes, and serum S100A9 levels. sRAGE levels were negatively associated with serum levels of C-reactive protein (CRP) and high-density lipoprotein (HDL), history of vasculitis, and the presence of the RAGE 82Ser polymorphism.
sRAGE and S100 proteins were associated not just with RA inflammation and autoantibody production, but also with classical vascular risk factors for end-organ damage. Consistent with its role as a RAGE decoy molecule, sRAGE had the opposite effects to S100 proteins in that S100 proteins were associated with autoantibodies and vascular risk, whereas sRAGE was associated with protection against joint and vascular damage. These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients.
晚期糖基化终末产物受体（RAGE）是细胞表面受体分子免疫球蛋白超家族的成员。在类风湿关节炎（RA）患者的血清和滑液中发现其三种假定的促炎配体，即S100A8/A9复合物（钙卫蛋白）、S100A8和S100A12的浓度较高。相比之下，可溶性RAGE（sRAGE）可能通过充当诱饵来预防促炎作用。本研究评估了RA患者血清中S100A9、S100A8、S100A12和sRAGE的水平，以确定它们与炎症以及关节和血管损伤的关系。
采用酶联免疫吸附测定法（ELISA）检测138例确诊RA患者和44例健康对照者血清中sRAGE、S100A9、S100A8和S100A12的水平，并通过非配对t检验进行比较。在RA患者中，通过简单和多元线性回归分析这些指标与疾病活动度和严重程度变量之间的关联。
RA患者血清中S100A9、S100A8和S100A12水平呈相关性。S100A9水平与体重指数（BMI）以及S100A8和S100A12的血清水平相关。S100A8水平与S100A9的血清水平、抗瓜氨酸化肽抗体（ACPA）的存在以及类风湿因子（RF）相关。S100A12水平与ACPA的存在、糖尿病史以及血清S100A9水平相关。sRAGE水平与血清C反应蛋白（CRP）水平、高密度脂蛋白（HDL）水平、血管炎病史以及RAGE 82Ser多态性的存在呈负相关。
sRAGE和S100蛋白不仅与RA炎症和自身抗体产生有关，还与终末器官损伤的经典血管危险因素有关。与其作为RAGE诱饵分子的作用一致，sRAGE与S100蛋白具有相反的作用，即S100蛋白与自身抗体和血管风险相关，而sRAGE与预防关节和血管损伤相关。这些数据表明，RAGE活性影响类风湿关节炎患者关节和血管疾病的共同发展。
