| ObjectivesTo determine the potential changes of Th17/Tfh cytokines IL-6,IL-17 A and IL-21 levels during induction therapy,and assess their relation with disease activity and immunologic features,explore the role of them in the development of LN.Methods1.28 patients with active lupus nephritis(SLEDAI≥5)admitted to the department of Rheumatology,The First Affiliated Hospital of Zhengzhou University from Jan of 2016 to Apr of 2017 were recruited in our study.Demographic,clinical and serological data were collected and disease activity were assessed at week 0,12,and 24.2.Serum concentrations of IL-17 A,IL-6 and IL-21 at week 0,12,and 24 were measured by cytometric bead array.3.Statistical analysis was performed using SPSS statistics software(version21).The quantitative parametric data were presented as Mean ± Standard Deviation(SD).Spearman rank correlation analysis was used to assess the relationship among the serum concentrations of IL-6,IL-17 A and IL-21,the SLEDAI score and laboratory parameters of LN patients.One-way ANOVA was used to analyze serum levels of IL-6,IL-17 A and IL-21 levels in different treatment groups(NR,PR and CR).The validity of IL-6,IL-17 A and IL-21 as a predictor of disease activity and remission was estimated by Receiver Operator Characteristics(ROC)curves,area under curve(AUC),cutoff point sensitivity,and specificity with 95% confidence intervals(CIs).The statistical differences were considered significant when P < 0.05.Results1.Alterations of serum cytokines in LN patients during induction therapy: A significant decrease in the serum IL-6 and IL-21 concentrations was observed after induction treatment.The mean level of serum IL-6 and IL-21 was significantly higher at week 0 compared to that at week 12(23.78±17.86 pg/ml vs 12.16±10.88 pg/ml,P=0.001;27.25±16.50 pg/ml vs 17.26±11.15pg/ml,P =0.001),and there was a further decline in the level of IL-6 and IL-21 at week 24(7.78±5.37 pg/ml,P <0.001;11.03±9.74 pg/ml,P =0.001);The mean level of serum IL-17 A at week 12 was lower than that at week 0,but there was no statistical significance(2.90±3.23 pg/ml vs5.03±4.90 pg/ml,P =0.077),However,its level was significantly decreased at week24 compared to that at week 0(1.56±1.85 pg/ml,P =0.006).2.The levels of IL-6,IL-17 A and IL-21 in NR,PR and CR groups: The level of IL-6 and IL-21 were lower in CR group when compared to the NR group(6.14±3.64pg/ml vs 12.90±5.49 pg/ml,P =0.012;8.70±8.43 pg/ml vs 21.72±8.57 pg/ml,P=0.018),but there no statistical significance when compared to PR group.A decline trend for IL-17 A was found,but no statistical significance.3.Correlations between cytokines levels and laboratorial parameters: The serum level of IL-6 was positively correlated with SLEDAI score(r =0.248,P =0.023),proteinuria(r=0.400,P <0.001),the titers of ANA(r=0.259,P=0.018),and serum C3(r =-0.270,P =0.013).Similarly,the serum level of IL-17 A was correlated with SLEDAI score(r =0.261,P= 0.016),proteinuria(r =0.254,P =0.020),and ANA(r=0.210,P =0.048).Such correlations was also found among the serum level of IL-21,SLEDAI score(r =0.252,P =0.021),proteinuria(r =0.220,P =0.045),and ANA(r=0.334,P <0.05).Somewhat surprisingly,no significant correlations were detected between these cytokines and serum C4 level.4.Correlations between serum IL-17 A and IL-6,IL-21 concentrations in lupus nephritis patients: There was a positive correlation between IL-17 A and IL-6,IL-21 concentrations in patients with LN(r =0.454,P <0.001)and(r =0.440,P <0.001).We also found strong correlation between IL-21 and IL-6 serum concentrations in patients with LN(r =0.342,P =0.001).5.ROC curve analysis: ROC curve analysis for IL-6,IL-17 A and IL-21 was performed in order to predict the disease activity showed that the optimal cutoff level being 5.78 pg/ml,1.98 pg/ml and 8.59 pg/ml,with AUC = 0.809,0.735 and 0.786.Both IL-6 and IL-21 concentrations may be used as the indicators of the remission of active lupus nephritis,with cutoff value at 9.12 pg/ml and 11.30 pg/ml,AUC= 0.930 and 0.896.ConclusionsThe production of serum IL-6,IL-17 A and IL-21 in active LN were dramatically declined during induction therapy,which may improve disease activity and delay disease progression of LN. |
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