Immunopathogenesis of idiopathic nephrotic syndrome in children: two sides of the coin

Chen, Jing; Qiao, Xiuying; Mao, Jianhua

doi:10.1007/s12519-020-00400-1

Cited by 18 publications

(9 citation statements)

References 71 publications

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“…The pathogenesis of nephrotic proteinuria in MCD is complex and still not fully elucidated, as evidenced by the emergence of new hypotheses [ 10 ]. The earliest, from the 1970s, suggested that circulating protein permeability factors released by dysfunctional T lymphocytes were responsible for the development of proteinuria in MCD [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Involvement of Hemopexin in the Pathogenesis of Proteinuria in Children with Idiopathic Nephrotic Syndrome

Pukajło-Marczyk

Zwołińska

2021

JCM

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Hemopexin (Hpx) is considered a factor in the pathogenesis of idiopathic nephrotic syndrome (INS). The aim of the study was to evaluate the serum and urine values of Hpx (sHpx and uHpx) in children with INS, analyze the role of Hpx, and assess its usefulness as a marker of the disease course. 51 children with INS and 18 age-matched controls were examined. Patients were divided into subgroups depending on the number of relapses (group IA—the first episode of INS, group IB—with relapses) and according to method of treatment (group IIA treated with gluco-corticosteroids (GCS), group IIB treated with GCS and other immunosuppressants). Hpx concentrations were determined by enzyme-linked immunosorbent assay (ELISA). sHpx and uHpx values in relapse were elevated in the whole INS group versus controls (p < 0.000). In remission their levels decreased, but still remained higher than in the control group (p < 0.000). In group IB uHpx levels were increased during remission as compared to group IA (p < 0.006). No significant impact of immuno-suppressants on sHpx was observed, but uHpx excretion in group IIA was higher in relapse (p < 0.026) and lower in remission (p < 0.0017) as compared to group IIB. The results suggest the role of Hpx in the pathogenesis of INS. Hpx may be a useful indicator for continuation of treatment, but it requires confirmation by further controlled studies.

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Section: Introductionmentioning

confidence: 99%

Involvement of Hemopexin in the Pathogenesis of Proteinuria in Children with Idiopathic Nephrotic Syndrome

Pukajło-Marczyk

Zwołińska

2021

JCM

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“…A large amount of data indicates that T cells and B cells are major participants in the pathogenesis of INS. The dysfunction or abnormal regulation of T lymphocytes is related to the pathogenesis of INS [ 7 ]. CD4 and CD8 cells play an important role in aiding and regulating immunity by releasing cytokines and other inflammatory mediators, which lead to renal injury.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have indicated that the most pathological process of INS is caused by T lymphocytes dysfunction or abnormal secretion of a capillary porousness factor [ 7 ]. Studies have found that peripheral blood CD3 + , CD4 + , CD4 + /CD8 + and IgG/IgM are decreased in children with NS [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood lymphocyte subsets in children with nephrotic syndrome: a retrospective analysis

Deng

et al. 2023

BMC Nephrol

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Background Nephrotic syndrome (NS) in children is widely believed to be associated with severe changes in the immune system. Based on lymphocyte subset analysis, we examined the pathogenesis of immune deficiencies in children with NS with varying steroid sensitivity. Methods Our study utilized flow cytometry to retrospectively analyze the ratios of lymphocyte subsets in 204 children with nephrotic syndrome and 19 healthy children. Results Compared with healthy children, the ratio of CD4 + /CD8 + in onset and remission was decreased in SRNS group (p < 0.05), and CD19 + B lymphocytes were increased in onset (p < 0.05). Compared with onset, the proportion of CD19 + B lymphocytes decreased in SRNS, while the proportion of CD19 + B lymphocytes increased in SDNS, p < (0.01). The ratio of CD8 + T/CD19 + B in onset in SDNS group was significantly higher than that in SSNS and SRNS groups (p < 0.01) and healthy control group (p < 0.05). Compared with onset, the ratio of CD8 + T/CD19 + B in SDNS group decreased significantly (p < 0.01), while the ratio of CD8 + T/CD19 + B in SRNS group increased significantly (p < 0.01). The proportion of CD56 + CD16 + NK cells was significantly reduced in children with INS (p < 0.01). Conclusion CD8 + T lymphocytes may be involved in the mechanism of lymphocyte subsets disorder during onset of SDNS, while CD19 + B lymphocytes may be involved in the mechanism of lymphocyte subsets disorder during relapse of SDNS. The CD8 + T/CD19 + B ratio may predict the degree of frequent recurrence. There is a certain degree of lymphoid subsets disorder in children with NS.

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“…Thus researchers suggest that anti-MIF therapies may be most effective in patients with high-expression MIF genotype (5). Immune dysregulation plays a crucial role in the pathogenesis of most INS patients (22). Cuzzoni et al observed that plasma MIF levels are significantly higher in INS patients before steroid treatment than in healthy controls (23).…”

Section: Discussionmentioning

confidence: 99%

Association Between Macrophage Migration Inhibitory Factor -173 G>C Gene Polymorphism and Childhood Idiopathic Nephrotic Syndrome: A Meta-Analysis

et al. 2021

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Background: Studies have identified that MIF -173 G>C gene polymorphism is associated with idiopathic nephrotic syndrome (INS) susceptibility and steroid resistance, but the results remain inconclusive.Methods: We searched PubMed, Embase, and Web of Science for relevant studies published before 31 March 2021. Pooled data were reported as odds ratio (OR) with 95% confidence interval (CI). Noteworthiness of significant OR was estimated by the false positive report probability (FPRP) test. Trial sequential analysis (TSA) was used to control type I and type II errors.Results: We selected seven case-control studies that included 1,026 INS children (362 were steroid-resistant NS and 564 were steroid-sensitive NS) and 870 controls. The results showed that MIF -173 G>C polymorphism was significantly associated with INS susceptibility in allelic, heterozygous and dominant genetic models (C vs. G: OR = 1.325, 95% CI: 1.011-1.738; GC vs. GG: OR = 1.540, 95% CI: 1.249-1.899; CC + GC vs. GG: OR = 1.507, 95% CI: 1.231-1.845), and FPRP test and TSA indicated that the associations were true in heterozygous and dominant models. The pooled results also revealed that MIF -173 G>C polymorphism was significantly associated with steroid resistance in allelic, homozygous and recessive models (C vs. G: OR = 1.707, 95% CI: 1.013-2.876; CC vs. GG: OR = 4.789, 95% CI: 2.109-10.877; CC vs. GC + GG: OR = 4.188, 95% CI: 1.831-9.578), but FPRP test indicated that all these associations were not noteworthy. Furthermore, TSA revealed that the non-significant associations between MIF -173 G>C polymorphism and steroid resistance in heterozygous and dominant models were potential false negative.Conclusions: This meta-analysis could draw a firm conclusion that MIF -173 G>C polymorphism was significantly associated with increased INS risk in heterozygous and dominant genetic models. MIF -173 G>C polymorphism was not likely to affect steroid responsiveness, but more studies were needed to confirm.

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Immunopathogenesis of idiopathic nephrotic syndrome in children: two sides of the coin

Cited by 18 publications

References 71 publications

Involvement of Hemopexin in the Pathogenesis of Proteinuria in Children with Idiopathic Nephrotic Syndrome

Involvement of Hemopexin in the Pathogenesis of Proteinuria in Children with Idiopathic Nephrotic Syndrome

Peripheral blood lymphocyte subsets in children with nephrotic syndrome: a retrospective analysis

Association Between Macrophage Migration Inhibitory Factor -173 G>C Gene Polymorphism and Childhood Idiopathic Nephrotic Syndrome: A Meta-Analysis

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