The Expression Of HMGB1 And RAGE In Lupus Nephritis Patients And The Effect Of Glucocorticoid

Background and ObjectiveSystemic lupus erythematosus(SLE),one of autoimmune disease, involves in multiple system organ. The pathogenesis is complicated,lupus nephritis(LN) is the leading cause of death in SLE patients. High mobility group box protein B1(HMGB1) is a kind of chromatin proteins, when released to outside the cell and as a kind of advanced proinflammatory cytokines, it stimulate the cytokines release. Receptor for advanced glycation end products(RAGE) is the major receptor of HMGB1. After combination of them, they mediated a series of inflammation by the activation of NF-kB. This aim of study explores the role of HMGB1 and RAGE in the pathogenesis of LN by detecting their expression in LN patients. At the same time we observed the effect of glucocorticoid(GC) on the expression of HMGB1 in LN which may provide a new view for the treatment.MethodsThe serum and urine samples of 64 SLE hospitalized patients in Nephrology Department, Rheumatology Department and Dermatology of the First Affiliated Hospital of Anhui Medical University from April, 2013 to June, 2014 were recruited in the study. The 64 patients all met the diagnose critenia of American Rheumatism association(ARA) about SLE. 10 health people were signed as normal controls. The serum and urine levels of HMGB1 were assessed by enzyme-linked immuno sorbent assay(ELISA) in SLE patients and normal controls. Among 64 SLE patients,25 patients were diagnosed lupus nephritis by kidney biopsy, including 6 II LN,4 III LN, 10 IV LN and 5 IV+V LN. Controls were taken from healthy parts of renal tissue from 10 tumornephrectomies. Immunohistochemistry was used to detect the renal tissue expressions of HMGB1 and RAGE in patients and healthy controls.(1)According to systemic lupus erythematousus activity index(SLEDAI),we make the SLE patients into two groups, active groups(SLEDAI≥10;serum:n=47;urine:n=33) and inactive groups(SLEDAI<10;serum:n=17;urine:n=14), then the differences of HMGB1 levels between this two groups were compared.(2) As routine urine appear hematuria(RBC>5/HP)、tube type or proteinuria(24h urine protein quantitative>0.3g or +++) for lupus kidney damage, we make the SLE patients into two groups, lupus nephritis groups(serum:n=37;urine:n=28) and lupus unnephritis groups(serum:n=27;urine:n=19). then the differences of HMGB1 levels between this two groups were compared.(3) According to the time of prednisone therapy, the LN patients that haven’t received any treatment(n=11) or received glucocorticoid therapy more than 2 weeks(n=13) were selected from LN patients. The effect of glucocorticoid therapy on the expression of HMGB1 in LN patients was analyzed.Results(1) The serum levels of HMGB1 were significantly higher in SLE patients compared to healthy controls(P<0.01).In patients with active disease compared to those with inactive disease(P<0.05),serum levels of HMGB1 were found to be significantly higher in patients with renal involvement compared to those without renal involvement(P<0.05).In addition, the levels of serum HMGB1 showed positive correlation with SLEDAI and urine protein(24 h)(r=0.26,P<0.05;r=0.55,P<0.05).(2) The urine levels of HMGB1 were significantly higher in SLE patients compared to healthy controls(P<0.01),in patients with active disease compared to those with inactive disease(P<0.05),urine levels of HMGB1 were not found to be significantly higher in patients with renal involvement compared to those without renal involvement(P>0.05).In addition, the levels of urine HMGB1 showed positive correlation withSLEDAI(r=0.35,P<0.05).(3) Intermediate-intensity staining of HMGB1 and RAGE were detected in renal tubules in normal-appearing renal tissues, however, both renal tubules and glomerular cells had the strong expression of HMGB1 and RAGE in SLE patients. The intrarenal production of HMGB1 and RAGE in SLE patients were obviously higher than that in normal-appearing renal tissues(P<0.05), and the expression levels of HMGB1 in SLE IV and IV+V were higher than those in SLE II(P<0.05), the expression levels of RAGE in SLE IV were higher than those in SLE II(P<0.05).(4) The serum levels of HMGB1、SLEDAI scores and the activity index of renal biopsy in LN patients which GC therapy were obviously lower than those in LN patients(P<0.05).ConclusionThe expressions of HMGB1 and RAGE in SLE patients were increased markedly. The levels of HMGB1 and RAGE showed a positive correlation with SLEDAI and urine protein(24 h). the change of HMGB1 and RAGE intrarenal expression level were associated with the classification of LN. The effect of glucocorticoid therapy in LN patients may be related to decrease of HMGB1...