The Role Of Tfh In Decreased Plasma IgG Of Pediatric Idiopathic Nephrotic Synndrome

Objective: To investigate the possible role and mechanism of Tfh in hypogammaglobulinemia of pediatric idiopathic nephrotic syndrome.Methods: 40 children with steroid-sensitive INS were enrolled in the study,and another 20 age and sex matched healthy children were served as control group.The children with steroid-sensitive INS were divided into 2 groups: new on-set group and remission group.The proportions of CD4+CXCR5+ICOShigh(Tfh)cells and CD27-Ig D+?CD27+Ig D+?CD27-Ig D-?CD27+Ig D-?CD27+Ig D-CD38 high B cells in peripheral blood were analyzed by flow cytometry.Real-time PCR was performed to analyze the gene expression of BCL-6,Blimp-1,m TOR,m TORC1,m TORC2,and IL-21.The plasma concentrations of IL-2,IL-21,and IL-6 were detected by ELISA.And the plasma concentrations of MDA were detected by colormetric analysis.After the T cells of new-onset INS patients cultured in plasma from healthy controls and plasma from new-onset INS patients,the proportions of CD4+CXCR5+ICOShigh(Tfh)cells in these cells were analyzed by flow cytometry,while the gene expression of m TOR and m TORC1 was detected by Real-time PCR.Results: Compared with healthy control group,(1)The proportions of Tfh cells were significantiy decreased in new on-set patients(P<0.05),but no obvious changes were observed in remission group(P>0.05);(2)The proportions of CD27+Ig D-B cells and CD27+Ig D-CD38 high B cells were remarkably decreased in new on-set group(P<0.05),but not changed in remission group(P>0.05);(3)The levels of Blimp-1,m TOR,m TORC1 expression in CD4+T was prominently up-regulated in new on-set group(P<0.05),while expression of BCL-6,IL-21 m RNA of CD4+T was notably down-regulated in new on-set group(P<0.05),but expression of m TORC2 was not significantly changed(P>0.05);(4)The concentrations of plasma IL-2 was remarkably increased in new on-set group(P<0.05),and the concentrations of plasma IL-21 andIL-6 didn't change significantly statistically even if there's a trend to decline(P>0.05);(5)Plasma concentrations of MDA was obviously increased in new on-set group(P<0.05),.and was not obviously changed in remiss group;(6)After cultured in normal plasma,the m TOR expression of INS CD4+T cells was prominently down-regulated(P<0.05),while the proportions of Tfh cells were significantly increased(P<0.05).Conclusion:(1)Disturbed differentiation of B cells resulted from downregulated proportions of Tfh cells maybe one of the factors for hypogammaglobulinemia in pediatric INS patients;(2)The imbalance of BCL-6/Blimp-1 caused by disordered cytokine milieu such as IL-2 and IL-21,and over-expression of m TOR(m TORC1)caused by hyperlipidaemia and IL-2 through PI3K-AKT singling pathway may be important cause leading to the down-regulated proportions of Tfh cells in pediatric INS patients?...