Study On The Relationship Between Macrophage Infiltration With Different Phenotypes In The Kidney And Podocyte Injury In Patients With Lupus Nephritis

Objective:To observe the infiltration of macrophages with different phenotypes of renal tissue in patients with lupus nephritis,to explore its role in podocyte injury in patients with lupus nephritis,and to provide noninvasive and reproducible indicators for the activity of patients with lupus nephritis and in patients with lupus nephritis.Methods : 60 patients diagnosed with lupus nephritis by renal biopsy and 10 normal people were selected to collect their relevant clinical data and serum and urine samples.Pathological changes of renal tissue by optical microscopy.The ultrastructure of kidney tissue such as podocytes was observed by electron microscope.The infiltration of macrophages(CD68)in renal tissue was observed by immunohistochemical staining.The change and distribution of macrophage phenotype(M1:iNOS+/CD68+;M2:CD206+/CD68+)in renal tissue were observed by immunofluorescence chemical double staining.Expression of podocyte-specific protein Nephrin in renal tissues was determined by immunofluorescence chemical staining.Serum and urine were collected and measured by indirect immunofluorescence chemical staining.Serum,urine macrophage-related immune indicators(IL-10 、IL-12 、TNF-α and OPN)and various activity indicators were determined using enzyme-linked immunosorbent assay.Results:Renal pathology in 60 patients with lupus nephritis showed 12 cases of type III lupus nephritis,18 cases of type IV lupus nephritis,16 cases of type V lupus nephritis and14 cases of type V+IV lupus nephritis.Of these,34 were active and 26 were inactive(defined as SLE disease activity according to the criteria of SLEDAI≥12).Expression of podocyte-specific protein Nephrin in renal tissues of lupus nephritis patients was significantly lower than that in normal control group,and type IV lupus nephritis was more significantly lower than type III,type V and type V+IV lupus nephritis(all P<0.05).The renal tissue macrophages of lupus nephritis showed abnormal activation and phenotypic regulation.The results of macrophage typing showed that the M1 and M2 infiltration of macrophages in renal tissue of lupus nephritis patients were increased and mainly type M2,and the macrophage infiltration degree of type IV lupus nephritis washigher than that of type III,type V and type V+IV lupus nephritis.There was significant correlation with clinical and pathological indexes of lupus nephritis patients.positively correlated with renal pathological activity index in lupus nephritis(P<0.05).Negatively correlated with podocyte Nephrin protein expression(P<0.05).The results showed that podocytes were not detected in normal human urine,podocyte abscission occurred in urine of patients with lupus nephritis,the positive rate of podocytes was about 85.2%,and the number of urine podocytes was positively correlated with 24 hours urine protein quantification and disease activity(all P<0.05),which was negatively correlated with the expression of glomerular podocyte-related protein Nephrin(P<0.05).The results indicated that podocyte-specific protein Nephrin was negatively correlated with macrophage(M1 and M2)infiltration,disease activity index and urine podocyte count(all P<0.05).The macrophage-related immune indexes(IL-10、IL-12、TNF-α and OPN)in serum and urine of lupus nephritis were higher than those of normal control group,and were statistically significant(all P<0.05).Conclusions : Macrophage infiltration with different phenotypes in kidney of lupus nephritis plays a vital role in podocyte injury and is associated with pathological activity.Local infiltration of macrophages in patients with lupus nephritis is associated with a variety of immune factors,which may be a potential mechanism of pathogenesis and predict disease activity in patients with lupus nephritis.