Expression Of Toll-like Receptor(TLR) 3 And 4 In Renal Tissues And Peripheral Blood Mononuclear Cells In Children With Idiopathic IgA Nephropathy

BackgroundImmunoglobulin A nephropathy,is the most common primary glomerulonehpritis,which is classically characterized by episodic hematuria associated with the deposition of IgA in the mesangium.For a number of years,nephrologests condidered it a benign nephropathy or disease with a very slow progression of renal damage.However,over the years it was observer that about 20%-40% of patients first described with IgAN went on to develop chronic renal insufficiency in 20 years,which is a serious threat to the quality of life of children and life.Therefore,it is necessary to carry out intervention treatment for patients with IgAN.However,because of the pathogenesis of IgAN is not fully understood,the treatment of IgAN is limited,so it is necessary to search the pathogenesis of IgAN.Several indications suggest a dysregulation of processing exogenous antigens derived from common pathogens,which can lead to abnormal immune response,aberrant IgA synthesis and renal damage,but the specific mechanism by which lead to the imbalance of immune system is still not clear.Toll like receptors(TLRs)is a novel and conserved pattern recognition receptor,which can be expressed in endothelial cells,immune cells and renal intrinsic cells.These receptors recognize both pathogen-associated molecular patterns and molecules that are released from damaged tissue.The TLRs-mediated signaling pathways consist of the myeloid differentiation factor 88-dependent pathway and TRIF-dependent pathway,both of which induce activation of nuclear factor κB,increase the expression of cytokines,chemokines,cell surface adhesion molecules and co-stimulatory molecules which subsequently leads to actication of antigen-specific adaptive immunity.In recent years,TLRs has become the focus of infection or non nephropathy study on infection.Wehave studied the expression of TLR4 and TLR7 in renal tissues of children with primary nephrotic syndrome,and confirmed that TLR4 and TLR7 play an important role in the pathogenesis of primary nephrotic syndrome in children.Does IgAN have abnormal changes in TLRs,is it involved in the pathogenesis of IgAN?ObjectiveTo investigate the expression and clinical significance of Toll-like receptor 3 and 4 in peripheral blood mononuclear cells and renal tissues of children with idiopathic IgAN,to procide experimental basis for the pathogenesis of IgAN,and to provide new ideas for the treatment of IgAN.Methods34 children with idiopathic IgAN were included as IgAN group,confirmed by renal biopsy,from First Affiliated Hospital of XinXiang Medical University,from September2014 to June 2016.In the same period,7 cases with renal tumor underwent nephrectomy in our hospital ascontrol group A,10 cases of healthy children as control group B,the expression of TLR3 and TLR4 in renal tissue were detected by immunohistochemistry method between IgAN group and control group A,and the positive expression rate of TLR3 and TLR4 in peripheral blood mononuclear cells were detected by flow cytometry method between IgAN group and control group B.The positive expression of TLR3 and TLR4 in renal tissue and peripheral blood mononuclear cells between IgAN group and control group was compared,to analyze the significance of TLR3 and TLR4 in the pathogenesis of IgAN.Results1.Expression of TLR3 and TLR4 in peripheral blood mononuclear cells: TLR3 was almost no expression in the peripheral blood mononuclear cells of the control group B.TLR3 showed a high expression in peripheral blood mononuclear cells of group IgAN.TLR4 showed a small amount of expression in peripheral blood mononuclear cells of the control group B.The expression of TLR4 in peripheral blood mononuclear cells of IgAN group increased significantly.The positive expressionof TLR3 and TLR4 of IgAN group in peripheral blood mononuclear cells were respectively(17.62 ± 8.33)% and(23.85±11.82)%,while the expression were respectively(0.31±0.06)and(3.02 ± 0.09)% in the control group B,the difference were statistically significant(P<0.05).2.Expression of TLR3 and TLR4 in renal tissue: The expression of TLR3 and TLR4 in renal tissue was expressed in nucleus and cytoplasm,respectively.In the control group A there was a little TLR3 expression in renal tubular epithelial cells and no TLR3 expression in the glomerular;TLR4 was not expressed in the renal tubules epithelial cells and glomerular.In group IgAN,TLR3 and TLR4 were highly expressed in renal tubular epithelial cells,but there were different degrees of TLR3 and TLR4 expression in glomerular mesangial cells.The expression of TLR3 and TLR4 in renal tissue of IgAN group were respectively(68.28±6.37)% and 0.048 ± 0.018,which were significantly higher than that in the control group A TLR3((9.69 ± 11.02)%)and TLR4(0.003 ±0.001),the difference were statistically significant(P<0.05).Conclusions1.The expression of TLR3 and TLR4 in renal tissue and peripheral blood mononuclear cells of IgAN were increased,suggesting that the abnormal activation of TLR3 and TLR4 may be involved in the pathogenesis of IgAN.2.According to the ligands of TLR3 and TLR4 identified,we concluded that viral and bacterial infections may lead to kidney damage in IgAN patients by immunization.