Clinical And Pathological Analysis Of IgA Nephropathy In Children And Induction Of Pluripotent Stem Cells In A Child With IgA Nephropathy

Objective To investigate the clinical and pathological characteristics of IgA nephropathy(IgAN)in children and correlations during biopsy.Methods The clinical manifestations,pathological characteristics and correlation of 66 children with IgA nephropathy diagnosed by renal biopsy were analyzed retrospectively from July 2017 to December 2020 in Guangzhou Women’s and children’s medical center.Results Among the 66 patients,44 were male(67%)and 22 were female(33%),The male to female ratio was 2:1,the average age was(7.74 ± 2.6)years old.(1)50 cases had hematuria and albuminuria(83%),15 cases had hematuria,only one had albuminuria;(2)10 cases(15%)had a family history of kidney disease;(3)Among the pathological grades,pathological changes were mainly grade Ⅲ(39 cases,59%);(4)According to Oxford-MEST score,the proliferation of mesangial cells accounted for 88%,and the proliferation of capillary cells accounted for 41%;(5)There were significant differences in the distribution of pathological grades among children with different clinical types,(p<0.05);(6)We found positive correlations between Lee grades with quantitative of 24-hour urinary protein(24h-UP),urine protein-creatinine ratio,blood urea nitrogen(BUN),serum creatinine,serum cystatin C among IgA nephropathy(IgAN)in children(allp<0.05),and negatively correlated with glomerular filtration rate.Conclusion IgAN has significant heterogeneity,clinical manifestations are diverse,clinical classification is related to pathological grade,24h-UP,urine protein-creatinine ratio,serum creatinine,serum cystatin C,BUN,glomerular filtration rate can predict the degree of renal pathological damage.Objective IgA nephropathy(IgAN)is a common glomerular disease at home and abroad.However,the exact pathogenesis of IgAN is still unclear.Induction of pluripotent stem cells in IgAN patient will provide a powerful cell model for studying the pathogenesis of IgAN.Method Generation of induced pluripotent stem cells(iPSCs)from peripheral blood mononuclear cells(PBMCs)of a IgAN patient by expressing five factors OCT3/4,SOX2,KLF4,c-MYC and Bcl-XL.IgAN-iPSCs were characterized by alkaline phosphatase staining(AP),karyotype analysis,RT qPCR,immunofluorescence,trilineage differentiation in vitro,integration analysis,and Mycoplasma test.Results We successfully generated iPSC from a IgAN patient.PBMCs-derived iPSC exhibited properties of human embryonic stem cells,including alkaline phosphatase staining was positive,RT-q PCR and immunofluorescence showed pluripotency gene expression,karyotype analysis showed normal karyotype(46,XY),and could differentiate into three germ layers.The derivation of IgAN-iPSC had no integration of exogenous factors and was negative for Mycoplasma.Conclusion The data showed that iPSC derived from PBMCs in IgAN patient has been successfully established for the first time,which can be used as a cell model for IgAN research and promote the in-depth understanding of the pathophysiology and pathogenesis of IgAN.