Association Of Increased Serum Renalase,Serum IL-34 And Serum IL-33 Levels With Disease Activity And Pathogenesis In Lupus Nephritis

Objective: Lupus nephritis(LN)is among the most serious complications of systemic lupus erythematosus(SLE),which causes significant morbidity and mortality,and which shows hematuria,proteinuria,eventually progress to renal insufficiency.Kidney damage mechanism of SLE are not fully understood and Currently in LN treatment is still the traditional glucocorticoids and immunosuppressive therapy,and while there have been some biological agents and targeted therapies,but the results are still not satisfactory.Many studies have implicated macrophages as actively contributing to LN pathogenesis in both human and murine disease.Renalase is a novel,kidney secreted cytokine-like protein that promotes cell survival and Involves cell damage and inflammatory reaction.Many studies have shown that renalase play an important role in organ transplantation and autoimmune diseases,and found its infiltration of macrophage-related.interleukine-34(IL-34)is a tissue-restricted ligand of colony-stimulating factor-1 receptor(CSF-1R)required for the development of macrophage and Promoting the secretion of inflammatory cytokines,and Involve in the regulation of innate immunity,humoral and cellular immunity.Studies have shown that IL-34 played an important role in the pathogenesis of autoimmune diseases.Interleukin-33(IL-33),a novel number of the IL-1 family With a similar biological effect of IL-1 and HMGB1,has been reported to have proinflammatory effects.Currently,Although Lots of studies have shown that renalase,IL-34 and IL-33 played an important role in the pathogenesis of autoimmune diseases,the association of renalase,IL-34 and IL-33 levels with Disease Activity and pathogenesis in LN has remained unknown.Here,we aimed to investigate the relationship of serum renalase,IL-34 and IL-33 levels with LN and its role in the disease progression of LN and to provide a theoretical basis for a new targets for therapy or other treatment methods in LN.Methods: This research includes 30 LN patients and 30 chronic glomerulonephritis patients and another 30 health adults from the first affiliated hospital of Dalian Medical University.At the same time other laboratory indexes were detected and the relation between the change of serum renalase,IL-34 and IL-33 levels and other indexes including Renal pathological damage and Laboratory test results were analyzed.The data are analyzed by t test,Chi-square test and Spearman correlation analysis by using SPSS.22.0,P<0.05 represents statistical significance.Results: 1.The level of serum renalase in LN group was obviously higher than that in chronic glomerulonephritis and healthy control [(181.676±44.269)ug/ml vs(76.317±24.950)ng/ml,P<0.05;(181.676±44.269)ng/ml vs(44.938±17.407)ng/ml,P<0.05)].The level of serum renalase in LN active group was also obviously higher than that in non-active group [(202.074±36.452)ng/ml vs(146.445±33.700)ng/ml,P<0.05].The levels of serum renalase in LN group showed negative correlation with the 1evel of serum albumin and C3(P<0.05),and showed positive correlation with24 hours protein quantification,ds-DNA,as well as the scores of CRP and SLEDAI(P<0.05).And the results also showed positive correlation with Glomerular proliferative,infiltration of inflammatory cells,as well as AI(P<0.05).It shows that serum renalase levels may have showed positive correlation with activity in lupus nephritis and have been involved in aggravating LN activities progress.2.The level of serum IL-34 in LN group was evidently higher than that in chronic glomerulonephritis and healthy control [(56.535±16.440)ng/L vs(31.754±14.176)ng/L,P<0.05;(56.535±16.440)ng/L vs(22.085±11.707)ng/L,P<0.05)].The level of serum IL-34 in LN active group was also obviously higher than that in non-active group [(61.647±14.204)ng/ml vs(47.703±14.204)ng/ml,P<0.05].The levels of serum IL-34 in LN group showed negative correlation with the 1evel of serum albumin and C3(P<0.05),and showed positive correlation with 24 hours protein quantification,ds-DNA,as well as the scores of CRP and SLEDAI(P<0.05).And the results also showed positive correlation with Glomerular proliferative and infiltration of inflammatory cells,as well as renal interstitial fibrosis and CI(P<0.05).It shows that IL-34 may have been involved in aggravating LN activities progress.3.The level of serum IL-33 in LN group was apparently higher than that in chronic glomerulonephritis and healthy control [(79.910±22.514)ug/L vs(42.899±21.790)ng/L,P<0.05;(79.910±22.514)ng/L vs(22.085±11.707)ng/L,P<0.05)].The level of serum IL-33 showed no relationship with active group and non-active group in LN [(82.908±22.301)ng/ml vs(74.730±22.982)ng/ml,P>0.05].The levels of serum IL-33 in LN group showed negative correlation with the 1evel of Hemoglobin,platelets,as well as serum albumin and C3(P<0.05),and showed positive correlation with 24 hours protein quantification,ds-DNA,as well as the scores of CRP and SLEDAI(P<0.05).And the level of serum IL-33 in Class V LN patients was obviously higher than proliferative LN(P<0.05).The results also showed positive correlation with Glomerular proliferative and infiltration of inflammatory cells,as well as renal interstitial fibrosis and CI(P<0.05).It shows that IL-33 may have been involved in aggravating LN activities progress.Conclusions: 1?The increase of serum renalase,serum IL-34 and serum IL-33 levels accelerates the development of lupus nephritis through inflammatory injury,while positively correlated with the change of pathology in active of lupus nephritis.2?The increase of serum IL-34 and serum IL-33 levels may be one of the most important risk factors of renal fibrosis in LN.3?Serum renalase and serum IL-34 would be good indirect serological potential markers in LN.