Serum Levels Of Interleukin-35 And Interleukin-17 In Patients With Lupus Nephritis

Backgrounds:Systemic lupus erythematosus(SLE)is a chronic,systemic disease of connective tissues that can affect any organs,but very often injures the kidney.Lupus nephritis(LN)is a major risk factor for overall morbidity and mortality in SLE.Although SLE exact etiology and mechanisms remain unclear,which involve multiple components of both the cellular and humoral immune system.Numerous inflammatory cells and cytokines are contributed to both onset and progression of renal pathology.These cytokines collectively play crucial roles in accelerating systemic inflammation,local tissue damage and immunoreactions.Interleukin-35(IL-35),belonging to the interleukin-12 family,has been identified as a novel anti-inflammatory cytokine.Interleukin-17(IL-17),belonging to the IL-17 family,is a pleiotropic pro-inflammatory cytokine.Recent studies reveal that both IL-35 and IL-17 are implicated in the pathogenesis of numerous autoimmune diseases.Furthermore,it has been suggested by several studies that the imbalance of regulatory T cells(Treg)and T helper 17(Th17),as well as its associated cytokines such as IL-35 and IL-17,play a pivotal role in the progression of SLE.Serum IL-35 levels,however,have not been studied in LN patients.The correlation between serum IL-35 and IL-17 in SLE patients has hardly been discussed to date.Moreover,the results are controversial about the correlation between serum IL-17 and disease activity in SLE patients.Objectives:The aim of the study was to determine serum IL-35 and IL-17 levels in SLE patients between active and inactive,and in SLE patients with and without nephritis,and their clinical values,and further investigate the relationship between serum IL-35 and IL-17.Methods:The study was carried out on 120 SLE patients.According to Systemic Lupus Erythematosus Disease Activity Index(SLEDAI),120 SLE patients were divided into active group(n = 65)and inactive group(n = 55).According to the standards of LN,120 SLE patients were divided into LN group(n = 80)and non-LN group(n = 40).We collected clinical data from 120 patients with SLE,including gender,age,body weight,duration of disease,anti-dsDNA antibodies,immune globulin,24-hour urine protein and so on.Serum immune globulin levels were determined by immunoturbidimetry.The parameters,including serum albumin(ALB),serum creatinine(Scr),blood urea nitrogen(BUN),blood uric acid(BUA),serum cystatin C(CysC),serum retinol-binding protein(RBP)were measured by spectrophotometry.Urine red and white blood cells(URBC,UWBC)were counted at high magnification.24-h proteinuria was also determined by immunoturbidimetry.Moreover,the serum levels of anti-dsDNA antibodies,IL-35 and IL-17 were detected by enzyme-linked immunosorbent assays(ELISA).Glomerular filtration rate can be estimated from serum creatinine using Cockcroft–Gault equations(eGFR).Analyses of data were performed the statistical package for the Social Sciences(SPSS)statistical software for Windows,Version 23.0.Results:(1)Active group have lower serum IL-35 levels compared to inactive group(P < 0.001).(2)Active group have higher serum IL-17 level,compared to inactive group(P = 0.001).(3)Serum IL-35 levels had negative correlations with SLEDAI(r =-0.626,P < 0.001),anti-dsDNA antibodies(r =-0.343,P = 0.001),erythrocyte sedimentation rate(ESR)(r =-0.354,P < 0.001)and had a positive correlation with complement 3(C 3)(r = 0.443,P < 0.001)in SLE patients.(4)Serum IL-17 was notably correlated with SLEDAI(r = 0.390,P < 0.001)in SLE patients.(5)A notable inverse correlation between serum IL-35 and IL-17 was observed in SLE patients(r =-0.339,P < 0.001).(6)Serum IL-35 levels were significantly lower in LN group(n = 80)than non-LN group(P = 0.013).(7)Serum IL-I7 levels were significantly lower in LN group than non-LN group(P = 0.012).(8)Serum IL-35 levels had positive correlations with ALB(r = 0.587,P < 0.001),eGFR(r = 0.348,P = 0.002),and had inverse correlations with Scr(r =-0.296,P = 0.008),BUN(r =-0.395,P < 0.001),BUA(r =-0.378,P = 0.001),CysC(r =-0.510,P < 0.001),URBC(r =-0.390,P < 0.001)and UWBC(r =-0.515,P < 0.001)in LN patients.(9)No significant correlations were found between serum IL-35 and RBP,24-h proteinuria in LN patients(P > 0.05).(10)Serum IL-17 was negatively correlated with ALB(r =-0.382,P < 0.001)and positively correlated with CysC(r = 0.322,P = 0.004)in LN patients.But there were no significant correlations between IL-17 and eGFR,RBP,24-h proteinuria in LN patients(P > 0.05).Conclusions:(1)There was a highly possible that the more IL-35 decreased,the more disease activity increased in SLE patients.(2)There was a highly possible that the more IL-17 increased,the more disease activity increased in SLE patients.(3)This study firstly found that serum IL-35 was negatively correlated with serum IL-17,indicating that keeping the balance of IL-35 and IL-17 in SLE patients is very important,which may have a potential significance in the alleviation of SLE.(4)This is the first study showing that decreased serum IL-35 level may indicate a high risk of renal damage in SLE patients.(5)The study found that decreased serum IL-17 in SLE patients did not necessarily indicate clinical remission,which may be a precursor of renal damage.(6)This is the first report that serum IL-35 may protect the charge barrier in glomerular basement membrane and have an advantage effect on restore glomerular selective filtration function,and alleviate renal damage.