The Significance Of Expression Levels Of NF-κB And HSP90 In Renal Needle Biopsy Tissues And Peripheral Blood Mononuclear Cells Of Lupus Nephritis Patients

Objective:Lupus nephritis(LN)is one of the severe forms of organ involvement in systemic lupus erythematosus(SLE)and is a major risk factor for high mortality in SLE.The pathogenesis of LN is still not well understood,as it involves autoantibody production,immune complex formation and deposition in the renal,followed by long-term inflammation,which causes damage to the structure and function of the renal.Nuclear factor-κB(NF-κB)is a broadly functional pro-inflammatory mediator.Heat shock protein 90(HSP90)is an important chaperone protein in humans.They both have been reported to be closely associated with various autoimmune diseases.In this study,the expression levels of NF-κB and HSP90 proteins and genes in renal needle biopsy tissues and peripheral blood mononuclear cells(PBMCs)of LN patients were examined to investigate their possible roles in the pathogenesis of LN patients.to provide.This study will provide more references for clinical diagnosis and the study of biologically targeted therapies for LN.Methods:52 renal needle biopsy tissues and their complete clinical data from patients diagnosed with lupus nephritis in our hospital from January 2016 to January 2022 were collected.32 renal specimens from hydronephrosis surgery and autopsy in our hospital from October 2020 to January 2022 were collected as the control group.The expression of NF-κB and HSP90 protein in glomerulus was detected respectively by Immunohistochemistry staining.In addition,16 patients with SLE,12 patients with LN and 16 healthy controls diagnosed in our hospital from January to August 2022 were collected.2.5 m L of fasting peripheral venous blood was collected respectively,and the gene expression levels of NF-κB and HSP90 in PBMCs of the subjects were detected by real-time fluorescence quantitative PCR technique.Results:1 The high expression rate of NF-κB and HSP90 in the glomerulus of LN patients was significantly higher than that in the control group High NF-κB protein expression was associated with severe lupus nephritis activity(SLEDAI > 15 points),elevated blood creatinine,decreased complement(C3,C4),and positive antids DNA antibodies(P < 0.05);it was not significantly correlated with increased uric acid and decreased GFR(P > 0.05)High expression of HSP90 protein was associated with severe lupus nephritis activity(SLEDAI > 15 points),decreased complement(C3,C4)and positive anti-ds DNA antibodies(P <0.05);no significant correlation with increased uric acid,increased blood creatinine and decreased GFR(P > 0.05).2 Compared with the control group,the expression levels of NF-κB and HSP90 m RNA were significantly upregulated in PBMCs of the SLE patient group(P < 0.05).3 The expression levels of NF-κB and HSP90 m RNA in PBMCs were significantly upregulated in the LN patient group compared with the SLE patient group(P < 0.05).4 The levels of NF-κB and HSP90 m RNA expression in PBMCs of the LN patient group were positively correlated(P < 0.05).5 The area under the ROC curve(AUC)for NF-κB m RNA expression in PBMCs from LN patients to diagnose SLE kidney damage was 0.929(95% confidence interval 0.833-1.000,P <0.001)and the AUC for HSP90 m RNA expression to diagnose SLE kidney damage was 0.742(95% confidence interval 0.556-0.927,P < 0.05).Conclusion:1 NF-κB and HSP90 are highly expressed in glomerulus of renal needle biopsy tissues of LN patients and are associated with some clinical features of LN.2 The expression levels of NF-κB and HSP90 m RNA were significantly higher in the SLE patient group compared to the control group,suggesting that NF-κB and HSP90 may be involved in the pathogenesis of SLE.3 Compared with the SLE patient group,the NF-κB and HSP90 m RNA expression levels were significantly higher in the LN patient group,suggesting that NF-κB and HSP90 may be involved in the process of LN kidney damage.4 The expression levels of NF-κB and HSP90 m RNA in the LN patient group were positively correlated,suggesting that NF-κB and HSP90 may play a synergistic role in the pathogenesis of LN.5 The AUCs of NF-κB and HSP90 expression in LN patients for the diagnosis of LN were 0.929 and 0.742,respectively,suggesting that high expression of NF-κB and HSP90 has a high diagnostic accuracy for diagnosis of LN or SLE without renal damage.It has important clinical application value.