Role Of Abnormal Glycosylated IgA1 And Interstitial Transformation Of Glomerular Endothelial Cells In The Development And Progression Of IgA Nephropathy

BackgroundIgA nephropathy(IgAN)is a series of clinical syndromes characterized by immunopathological features mainly in the mesangial region of the glomerulus and is a common primary renal disease in childhood.IgA nephropathy is a chronic progressive disease,and it is one of the main glomerular diseases that cause end-stage renal disease and chronic renal failure.About 25%to 30%of patients with IgA nephropathy develop varying degrees of renal failure within 20 to 25 years after the disease,requiring dialysis or kidney transplantation.At present,the etiology and pathogenesis of IgA nephropathy are not yet clear,and its poor prognosis seriously threatens the health of children and imposes a heavy burden on society.Therefore,it is of great significance to further clarify the etiology and pathogenesis of IgA nephropathy.The deposition of IgA in the kidney is not only an immunopathological feature of IgA nephropathy but also an important factor involved in renal injury.Most scholars believe that abnormal glycosylation of IgAl plays an important part in the pathogenesis of IgA nephropathy.Abnormally glycosylated IgA1 participates in the occurrence and development of IgA nephropathy in various ways,mainly depositing in the mesangial area of the kidney,stimulating the mesangial cells of the kidney to trigger a series of reactions and causing kidney damage.In recent years,endothelial-interstitial transformation(EndMT)has been found to play an important role in renal fibrosis.Studies have found that endothelial cells with EndMT will lose the expression of endothelial cell-specific proteins,like CD31/platelet endothelial cell adhesion molecule(PECAM-1),vascular endothelial cadherin(VE-cadherin),and at the same time,the expression of mesenchymal cell-specific genes in endothelial cells is activated.Expression and production of encoded proteins such as α-smooth muscle actin(α-SMA),vimentin,etc.Patients with IgA nephropathy will experience varying degrees of renal failure within a few years after the onset,and the occurrence and development of fibrosis have always been the focus of their research.We speculate that EndMT may also be involved in the occurrence and development of renal damage in IgA nephropathy.So far,there is no relevant research on EndMT in IgAN.PurposeTo investigate the level of abnormal glycosylated IgAl in blood and kidney of children with IgA nephropathy by detecting abnormal glycosylated IgA1 in blood and kidney of children with IgAN.The expressions of VE-cadherin,CD31,α-SMA,and vimentin were detected to investigate the interstitial transformation of glomerular endothelial cells in IgAN.And explore their roles in the development of IgA nephropathy provide new ideas and targets for clinical treatment of IgAN.MethodsCase group:20 children with IgA nephropathy who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University from 2019.10 to 2021.09 were selected;control group:blood samples from 20 children who underwent physical examination in our hospital during the same period were selected as the control group(A);10 cases of normal kidney tissue adjacent to cancer in children undergoing radical nephrectomy in the Pediatric Urology Department of our hospital were used as the control group(B).This experiment has been approved by the ethics committee review.The general clinical data of the children in the case group were collected:gender,age,urine routine(urinary protein,urine red blood cell count,etc.),24-hour urine protein,etc.,and the age and gender data of the control group were collected.Serum Gd-IgAl levels in the case group and control group(A)were measured by ELISA.The expression of Gd-IgAl,VE-cadherin,CD31,α-SMA,and vimentin in the kidney of the case group and control group(B)were detected by immunohistochemistry.Statistical analysis of experimental data was performed using SPSS 26.0 statistical software.Results1.The serum abnormal glycosylated IgA1 concentration of the case group was significantly higher than that of the control group(A),and the difference was statistically significant(P<0.05).Abnormally glycosylated IgA1 was not expressed in normal kidneys,but the glomerular abnormally glycosylated IgAl in the case group was positive.The serum concentration of abnormally glycosylated IgAl in the case group was not related to the deposition of abnormally glycosylated IgA1 in the kidneys.2.Compared with the children in the control group(B),the expression of CD31 in the renal glomerulus of the children in the case group was significantly decreased,and the expressions of α-SMA and vimentin were significantly increased.The difference between the two groups was statistically significant,and there was no significant difference in VE-cadherin surface density between the two groups.3.No significant correlation was found between the deposition of abnormally glycosylated IgAl in the kidney and the expression of VE-cadherin,CD31,α-SMA,and vimentin in the kidney.In the case group,CD31 was significantly negatively correlated with α-SMA,and α-SMA There was a significant positive correlation with vimentin and a significant negative correlation between CD31 and VE-cadherin.ConclusionAbnormally glycosylated IgAl molecules may promote the occurrence and development of IgA nephropathy,and the serum concentration of abnormally glycosylated IgAl cannot predict the degree of its deposition in renal tissue.The occurrence of endothelial cell-mesenchymal transition in the glomerulus of children with IgA nephropathy may be involved in the development of renal fibrosis in IgA nephropathy.