Clinical Significance Of Toll-like Receptor (TLR)4and TLR7Expressions On Renal Tissue In Children With Primary Nephrotic Syndrome

Background Primary nephrotic syndrome(PNS) is the common glomerular disease in children. About90%etiology of children PNS is unknown. Toll-like receptors(TLRs) belong to pattern recognition receptors. TLRs mediated pathogenesis of many renal infectious and non-infectious conditions. TLR4is confirmed to be the receptor of lipopolysaccharide(LPS). After binding to its receptors, TLR4activates nucleus factor-KB (NF-κB) and promotes release of inflammatory factors, which enhance the permeability of glomerular basement membrane and aggravate proteinuria. TLR7is confirmed to be the receptor of virus’s RNA. TLR7participates in B-cell survival, activation and autoantibody production depended upon MyD88-dependent signaling pathways,and it was known to play an important role in the development of SLE. At present, the research about TLR4and TLR7in children with PNS is seldom reported.Objective To explore expressions and clinical significance of TLR4、TLR7via immunohistochemistry in renal specimens from children PNS with bacterial infection or virus infection and analysis the interrelation among TLR4、TLR7and different types of renal pathology.Methods Expressions of TLR4and TLR7were examined in renal biopsy specimens from110PNS in children and21healthy controls by immunohistochemical method. According to the renal pathologic classification of PNS, the different TLR4and TLR7expressions in different renal pathology type of PSN were compared.Results1. Trace impression of TLR4in normal glomerulus and renal tubules was measured, Moreover impression level of TLR4in renal interstitium was more lower. The expression of TLR4in renal tubules was significantly increased in PNS children (P<0.01). However, there has no statistically significant in expressions in glomerulus and renal interstitium between PNS children and healthy controls (P>0.05).The expression level of TLR4may be correlated with different renal pathology type. Compared to the membranous nephropathy (MN),mesangial proliferation glomerulonephritis (MsPGN) and focal segmental glomerulosclerosis (FSGS), the highest expression of TLR4was observed in minimal change disease (MCD)(P<0.01).2. Insignificant expression of TLR7in glomerulus, renal tubules and renal interstitium were observed in normal kidney tissue. But expression level of TLR7was significantly increased in renal tubules of PNS children (P<0.01). TLR7impression in glomerulus and renal interstitium were no significant difference between PNS children and healthy controls (P>0.05). There is a direct correlation between Expression level of TLR7and different renal pathology. Compared to the MCD、MN and FSGS、the highest expression of TLR7was observed in MsPGN (P<0.01).Conclusions1. TLR4expression increased in renal tubule of children with PNS and may be correlated with different renal pathology type. Among MCD, MN, MsPGN and FSGS, expression of TLR4was the highest in MCD. And the expression of TLR4was lowest in FSGS.2. TLR7expression increased in renal tubules of children with PNS and its expression level may be correlated with different renal pathology type. Among different renal pathology such as MCD, MN, MsPGN and FSGS, expression of TLR7in MsPGN was the highest, the next is that in MN, and expression of TLR7in FSGS was the lowest.3. TLRs might participate in the pathogenesis of primary nephrotic syndrome in children.