Function of miR-24 and miR-27 in Pediatric Patients With Idiopathic Nephrotic Syndrome

Abstract

Purpose: We investigated the pathogenesis of idiopathic nephrotic syndrome (INS) by measuring the effects two specific miRNAs on Th2 cells in children with this disease.Methods: After informed consent, we enrolled 20 children with active INS before steroid initiation, 20 children with INS in remission after steroid therapy, and 20 age-matched healthy controls. Flow cytometry was used to measure the levels of Th2 cells and a cytometric bead array was used to measure the levels of IgE, interleukin (IL)−4, and IL-13. RT-PCR was used to measure the levels of miR-24 and miR-27 in CD4+TCD25− cells. PBMCs were isolated using Ficoll density gradient centrifugation, and transfected with different mimic or inhibitor miRNAs. RT-PCR was used to measure the expression of different RNAs, and flow cytometry was used to determine the percentage of Th2 cells.Results: Relative to healthy controls, children with active INS had higher percentages of Th2 cells (P < 0.05), but there was no significant difference in controls and children in remission. The plasma levels of IgE, IL-4, and IL-13 were significantly increased in children with active INS (P < 0.05). There were lower levels of miR-24 and miR-27 in children with active non-atopic INS (P < 0.05). Transfection experiments indicated that upregulation of each miRNA decreased the percentage of Th2 cells and the level of IL-4 (P < 0.05), and down-regulation of each miRNA had the opposite effects (P < 0.05).Conclusion: Children with active INS, with or without atopy, had higher levels of IgE, possibly related to their higher levels of IL-13 and IL-4 due to a drift toward Th2 cells. miR-24 and miR-27 suppressed the expression of Th2 cells and have a critical function regulating Th2 cell expression in INS.

Serum IgE level in children with Idiopathic Nephrotic Syndrome

“…In our study, the median serum IgE was significantly higher in group I (275.55IU/ml) than group II (100.5IU/ml). Our results were matched with Ni et al (6) , who reported that analysis of IgE concentration indicated significantly greater levels in the active phase (firstonset) group with atopic constitution (1350.67 ± 837.39 IU/mL, p < 0.05) and the active phase group with non-atopic constitution (441.01 ± 357.45 IU/mL, p < 0.05) than in the control group (57.76 ± 48.25 IU/mL). Also, Hossain (7) , reported that the mean serum IgE level of nephrotic syndrome in children was (537.98±52.56IU/ml) which was higher than controls (38 ± 18 kU/L), p (<0.05).…”

Serum IgE Levels Are Associated With the Prognosis of Minimal Change Disease

“…Though there were no significant differences in the history of allergy between the low- and high-IgE groups in this study, a higher percentage of eosinophilia was observed in the high-IgE group, indicating that the allergic condition may exist. Ni et al ( 20 ) and Cheung et al ( 21 ) reported that serum IgE levels of MCD patients were higher in the atopic subgroup than that in the non-atopic subgroup at the time of remission. We assessed the IgE levels when patients were in remission.…”

“…This indicates that the increase in serum IgE levels might be related to Th2 activation ( 29 , 30 ). Some evidence suggests that the Th2 cytokine, IL-13, may play a potential regulatory role in MCD pathogenesis and high serum IgE levels: multiple reports have shown that serum IL-13 levels in MCD patients are elevated; IL-13 can regulate IgE production; and IL-13 can induce glomerular podocyte damage in animal models and caused MCD-like pathological changes ( 11 , 20 , 21 ). Therefore, IL-13 may drive the onset of the nephrotic syndrome and the increase of serum IgE levels.…”