Changes And Significance With Th17/Treg In Peripheral Blood Of Idiopathic Membranous Nephropathy Patients

Background Idiopathic membranous nephropathy (Idiopathic membranous nephropathy, IMN) is an important pathologic types of idiopathic nephrotic syndrome, the pathogenesis is complex, which has not yet been completely elucidated. Previous studies showed that, podocyte target antigen was component of anionic in situ immune complex formation corresponding antibody, and complement system activation of neutrophils in the pathogenesis of the basilar membrane caused local damage. However, the phenomena in a large number of clinical and basic research in recent years can not be perfectly explained by the theory. With the development of imbalance hypothesis of the Treg/Thl7, the role in the pathogenesis of IMN is gradually payed extensive attention from scholars.Objective To observe the changes of Th17 and CD4+CD25+CD1271owTreg cells in peripheral blood of IMN patients, and the effect on the index after tacrolimus therapy. To explore the pathogenesis of IMN and to provide basis for reasonable application of tacrolimus in IMN.Method We included 20 cases membranous nephropathy patients who diagnosed with renal pathology and 24-hours urinary protein quantity being greater than or equal to 4g. Various secondary kidney disease were excluded.10 healthy volunteers were selected as control group. The helper T cell subsets (Treg, Th17) percentage in peripheral blood were assessed with flow cytometry. The plasma were collected to examine the expressions of cytokines levels using enzyme linked immunosorbent assay (ELISA) methods.To analyse the correlation between Th cell subsets, cytokines and the clinical indexes, and the changes of Treg and Thl7 cells and related cytokines in peripheral blood with IMN who received tacrolimus combined with glucocorticoid for treatment.Results(1) The expression changes of IL-17 and Th17:compared with control group, Th17 cell ratio and the expressions of IL-17 were elevated at every point:before treatment, treatment for 3 months,6 months(P<0.01). After 6 months treatment with tacrolimus, the expressions of IL-17 and Th17 were significantly lower (P<0.01);There were obviously significant differences of the above indexes between before treatment and 3 months of treatment (P< 0.01).(2) The expression changes of Treg and IL-10:compared with control group, Treg cell ratio and the expressions of IL-10 were decreased at every point:before treatment, treatment for 3 months,6 months(P<0.01). After 6 months treatment with tacrolimus, the expressions of Treg were significantly higher(P<0.01);There were obviously significant differences of Treg between before treatment and 3 months of treatment (P< 0.01), whereas there were no significant differences between IMN group and the control group for IL-10.(3) The changes of urinary protein, serum albumin level:compared with control group, the expressions of serum albumin level were elevated at every point:before treatment, treatment for 3 months,6 months(P<0.01). After treatment for 6 months, urinary protein levels in IMN patients were significantly reduced(P<0.01). There were obviously significant differences of above indexes between before treatment and 3 months of treatment (P< 0.01).(4) Correlation analysis:Th17 cell ratio and IL-17 were positively correlated with urinary protein in IMN patients (r=0.931; 0.921, P<0.01), and were negatively correlated with serum albumin (r=-0.891;-0.837, P<0.01). Treg cell ratios were negatively correlated with urinary protein in IMN patients (r=-0.827; P<0.01), and were positively correlated with serum albumin (r=0.857, P<0.01).Conclusion(1) There were obvious imbalance of Th17/Treg in IMN patients.(2) Tacrolimus combined with glucocorticoid therapy has positive control for Th17/Treg imbalance.