Expression And Significance Of ANCA In Serum And HMGB1 In Renal Tissue Of Patients With Lupus Nephritis

Objective: Lupus Nephritis(LN),a typical immune-complex mediated glomerulonephritis,is the most frequently accumulating organ in SLE and is an important cause of end-stage renal disease and death in patients.ANCA is an autoantibody against the neutrophils cytoplasmic component,mainly including anti-myeloperoxidase antibody(MPO-ANCA)and anti-protease 3 antibody(PR3-ANCA).Many studies have explored the clinical and renal pathologic characteristic of ANCA positive LN and ANCA negative LN,but few studies have focused on the relationship between the serum ANCA level and the clinicopathological characteristics of LN.High Mobility Group Box 1 protein(HMGB1),as a pro-inflammatory mediator,is associated with the activity of LN.Neutrophil extracellular traps(NETs)released by neutrophils to kill bacteria are composed of chromatin and granular proteins(e.g.MPO,PR3).In LN,the increased production and the decreased clearance of NETs leads to prolonged half-life of MPO and PR3 antigens,resulting in the production of MPO-ANCA and PR3-ANCA,and the formation of NETs is also associated with the activity of LN.At present,the formation mechanism of NETs in LN renal tissue is not completely clear,while in vitro experiments have found that HMGB1 can increase the production of NETs.Therefore,the purpose of this study is :(1)to analyze the relationship between ANCA titer in serum and the clinical and differrent renal pathological manifestitations of LN,and whether ANCA causes the production of LN through pauci-immune complex deposition(pauci-immune LN).(2)to explore the expression level of HMGB1 in the renal tissue of LN patients and analyze its relationship with neutrophil infiltration in renal tissue,ANCA titer and other clinical and renal pathological characteristics.Methods:(1)There are 119 LN patients according to the inclusive criteria,analyze the relationship of serum MPO-ANCA and PR3-ANCA titer and LN clinical indicators,pathological type and pathological damage,immune complex,complement deposition,analyze the positive rate of serum ANCA in pauci-immune LN and the clinical pathological features of them,discuss the relationship between ANCA positive and pauci-immune complex deposition of LN.(2)the expression of HMGB1 in renal tissue of LN patients was detected by immunohistochemistry,and the relationship between HMGB1 in renal tissue and neutrophils and serum ANCA titer was analyzed.Results:(1)The serum MPO-ANCA titer relat PR3-ANCA titer were negatively correlated with white blood cell count and serum complement C3 level in LN patients.The serum PR3-ANCA titer in LN with fibrogenic crescens is lower than in LN without fibrogenic crescens.In terms of immunoglobulin and complement deposition,serum PR3-ANCA level was positively correlated with IgA and C3 deposition in renal tissue.Serum PR3-ANCA level was higher in type IV than in non-type IV,III and V.ROC curve was used to analyze the diagnose effect of serum PR3-ANCA on type IV LN,with an AUC value of 0.653(< 0.7),a sensitivity of 63.1% and a specificity of 70.4%.(2)All the included 15 patients with pauci-immune LN were negative in terms of serum ANCA,and there was no difference in the expression levels of glomerular fibrinoid necrosis and crescens between the pauci-immune LN group and the non-pauci-immune LN group.There were significant deposits of immune complexes in all 17 LN patients with surm ANCA positive.(3)In patients with LN,HMGB1 expression in renal tissue was increased,and its level was negatively correlated with serum complement C3 and interstitial inflammatory cell infiltration,while HMGB1 expression in renal tissue was not correlate with neutrophils,and serum MPO-ANCA and PR3-ANCA titer.Conclusion :(1)The serum MPO-ANCA and PR3-ANCA titers were associated with blood complement C3 levels and platelets,and were associated with pathological types,pathological damage,and the degree of immune complex deposition.(2)In LN,ANCA does not cause disease in the form of oligoimmune complex deposition.(3)The expression of HMGB1 in LN renal tissue was higher than that in normal renal tissue,and its level was related to blood C3 and infiltration of renal interstitial inflammatory cells.