The Study On Association Between Serum SRAGE Level And Disease Activity Of Systemic Lupus Erythematosus

IntrodutionSystemic lupus erythematosus(SLE) is an autoimmune disease which affects multiple organs and systems and is characterized by the production of a variety of autoantibodies against its own nuclear antigens such as DNA, RNA and other nucleus composition. It is called as the prototype of the autoimmune diseases. This disease mainly affects women of child-bearing age and the male to female ratio is 1:9. Almost all organs can be involved during the course of SLE, such as skin, joint, kidney, brain, cardiovascular, gastrointestinal and so on. And the feature of alternating remission and relapse of this disease makes almost every patient with SLE need to accept life-long anti-lupus treatment, which brings huge financial burden and mental stress to the society and the patients themselves. However, the specific pathogenesis of the disease is so complex that it has not been fully elucidated so far. However, in recent years, the research of its pathogenesis has never been stopped, and some studies have shown that a wide range of molecules are involved in the duration of SLE and play an important role in its pathogenesis.Soluble receptor for advanced glycation end products(s RAGE) is the soluble form of cell surface RAGE(the receptor for advanced glycation end products). It is a kind of newly discovered protein which might play an important role in the pathogenesis of SLE. As a member of immunoglobulin superfamily[6], s RAGE can be formed by alternative splicing of RAGE m RNA[1-3] or it may come from proteolytically cleaved forms of cell surface RAGE by the action of matrix metalloproteinases MMP-9 or ADAM10[4,5]. It is a multiligand receptor which can bind a variety of endogenous ligands such as advanced glycation end products(AGEs), S100 proteins/calgranulins, high-mobility group box 1 protein(HMGB1), amyloid-beta peptide, beta2 integrin Mac-1 and so on[7-10]. As its structure is composed of only the extracelluar ligand-binding domain of RAGE, lacking the transmembrane domain and the short cytoplasmic tail, so s RAGE only has the function of ligand binding of cell surface RAGE but lacking its function of intracellular signal transduction. Therefore, s RAGE is called as “decoy” receptor because of this properity. Many research indicate that s RAGE can compete with cell-bound RAGE for ligand binding, block the nuclear transfermation of NF-κB and activation of downstream molecules such as tumor necrosis factorα(TNF-α), interleukin 6(IL-6) and so on, inhibit the celluar inflammatory cascade and thus protect these susceptible cells from the potential poison effect due to the activation of ligand-receptor signal pathway[6]. However, the feature of s RAGE and its specific mechanism of regulating inflammation is still unknown yet, and need to be further elucidated.Currently, the correlation research between sRAGE and disease characteristics of SLE has became a hot topic in the field of Rheumatology. People sought to investigate whether s RAGE could be a new biomarker of SLE to evaluate the disease activity. In spite of this, there is no unified understanding on the limited correlation research between serum s RAGE level and disease activity of SLE, and it still needs a large number of multicenter, randomized, double-blind, controlled studies to confirm. Our research aimed to find the correlation between serum s RAGE level and the disease activity of SLE as well as the relevant laboratory examinations, evaluate whether it could be a new biomarker of the disease, and eventually provide certain basis for individualized treatment plan.ObjectivesTo explore the association between serum sRAGE level and the disease activity of SLE.Methods1. 104 SLE patients admitted to the Rheumatology and Nephropathy outpatients and inpatients of the First Affiliated Hospital of Zhengzhou University in 2013.6-2014.6 were enrolled in our study. Information pertaining to demographic characteristics, clinical and laboratory data was collected from the medical record and blood samples were collected form all the participants. Preserved the supernatant at-80℃ in the fridge after centrifuged. 2. Detected concentration of serum s RAGE using enzyme-linked immuno sorbent assay(ELISA). All the patients were divided into two groups according to Systemic lupus erythematosus disease activity index(SLEDAI) scores. We defined patients with SLEDAI scores 0-4 as inactive SLE group, and patients with SLEDAI scores ≥5 as active SLE group. Analyzed the difference of serum s RAGE level between different groups; analyzed the correlation between serum s RAGE level and the clinical parameters as well as the disease activity of SLE. 3.Statistical analyses were performed by the Statistical Package for the Social Science(SPSS) 17.0 software(Chicago, Illinois, USA). Quantitative data were expressed using mean±standard deviation( x±s), and qualitative data were expressed using percentage(%). Nonparametric test(Mann-Whitney U test) were used to compare two quantitative data, and Spearman rank correlation analysis were used to evaluate the association between clinical prarmeters and serum s RAGE level. A p-value of <0.05 was considered statistically significant.Results1.Serum s RAGE level in active SLE group was significantly higher than that in inactive SLE group, and the difference was statistically significant(Z=-2.673,p=0.008). 2.The correlation analyses between serum s RAGE level and the clinical paremeters: there is positive correlation between serum s RAGE level and anti-ds DNA antibody titer(CI=0.268, p=0.008), 24 hours urinary total protein quantitative(CI=0.387, p=0.001) and SLEDAI scores(CI=0.373, p=0.000); there is negative correlation between serum s RAGE level and white blood cell count(CI=-0.230,p=0.020), complement C3(CI=-0.371, p=0.000) and complement C4(CI=-0.280, p=0.000).ConclusionsThere is positive correlation between serum s RAGE level and the disease activity of SLE. And serum s RAGE level may become a new biomarker evaluating disease severity of SLE.