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Transcriptome profile of leukocyte RNA from children with steroid sensitive and resistant nephrotic syndrome

ABSTRACT: Transcriptome profile of leukocyte RNA from children with steroid sensitive and resistant nephrotic syndrome

PROVIDER: PRJNA608900 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11185600.fastq.gz	Fastqsanger.gz
	SRR11185700.fastq.gz	Fastqsanger.gz
	SRR11185601.fastq.gz	Fastqsanger.gz
	SRR11185701.fastq.gz	Fastqsanger.gz
	SRR11185602.fastq.gz	Fastqsanger.gz

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Transcriptome profile of leukocyte RNA from children with steroid sensitive and resistant nephrotic syndrome

Project description:Glucocorticoid resistance complicates the treatment of ~20% of children with nephrotic syndrome, yet the molecular basis for resistance remains unclear. We generated the transcriptome profile by RNA sequencing of peripheral blood leukocytes from children obtained both at initial nephrotic syndrome presentation and after ~7 weeks of glucocorticoid therapy to identify genes or a gene panel able to differentiate steroid sensitive from steroid resistant nephrotic syndrome. RNA -seq analysis was followed by in-silico algorithm-based approaches and subsequent biochemical analyses on relevant candidate gene with important roles in podocyte and glomerular pathophysiology, using both patient samples and experimental models of nephrotic syndrome and podocyte injury.

2021-02-16 | GSE145969 | GEO

Urinary sediment mRNA level of CREBBP and CYBA in children with steroid-resistant nephrotic syndrome

Project description:This study aimed to evaluate gene expression patterns in urinary sediment samples of children with steroid-resistant nephrotic syndrome (SRNS).

2022-02-23 | GSE189734 | GEO

Pilot Plasma Proteomic Study of Steroid Resistance in Pediatric Nephrotic Syndrome

Project description:Pilot proteomic study of immunodepleted plasma samples comparing steroid sensitive and steroid resistant pediatric nephrotic syndrome patients.

2018-02-27 | MSV000082114 | MassIVE

The effect of serum from children with nephrotic syndrome on transcriptome of human immortalized podocytes cultured in vitro

Project description:Nephrotic syndrome (NS) is an unfavorable disease with heterogeneous causes and variable prognosis. One of the clinically crucial prognostic feature is the response to initial glucocorticoid treatment. Whereas in some children with steroid-sensitive nephrotic syndrome (SSNS) the treatment may induce long-term remission of the disease, steroid-resistant cases (SRNS) are at risk of renal failure requiring renal replacement therapy. The aim of this project was to explore whether sera from children with the two main clinically defined types of NS induce changes in transcriptome of in-vitro cultures of immortalized human podocytes. After 3 days of culture, total RNA was isolated and then library from polyadenylated RNA was prepared and RNA sequencing was performed. Log2 (fold-changes) were calculated to describe differential gene expression. Within the Reactome online tool, Camera methodology was implemented to identify functionally linked gene groups (pathways) that could distinguish the two patient groups. Significant transcriptome differences were found between samples from children with SSNS and SRNS. This may help to reveal the molecular mechanisms of the disease and open up for an effective individualized treatment.

2022-10-14 | GSE215231 | GEO

proteomic analysis of the formalin-fixed paraffin embedded (FFPE) renal tissue between steroid-sensitive and steroid-resistant (SR) children FSGS patients

Project description:In children, focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant nephroticsyndrome (SRNS). To identify specific candidates and the mechanism of steroid resistance, we examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Renal biopsies from seven steroid-sensitive (SS) and eleven steroid-resistant (SR) children FSGS patients were obtained. We examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, as well as the construction of protein-protein interaction (PPI) network were performed. Two proteins were further valiadated by immunohistochemistry staining in FSGS patients and mice models. In total, we quantified 4794 proteins, of which 325 were found to be differentially expressed proteins (DEPs) between the SS and SR group (foldchange ≥ 2, P＜0.05). The results of GO revealed that the most significant up-regulated proteins were primarily related to protein transportation, regulation of the complement activation process and cytolysis. Moreover, clustering analysis showed differences in the pathways (lysosome, terminal pathway of complement) between the two groups. Among these potential candidates, validation analyses for LAMP1 and ACSL4 were conducted. LAMP1 was observed to have a higher expression in glomerulus, while ACSL4 was expressed more in tubular epithelial cells.

2022-11-19 | PXD036164 | Pride

Urinary sediment mRNA level of CREBBP and CYBA in children with steroid-resistant nephrotic syndrome

Project description:Urinary sediment mRNA level of CREBBP and CYBA in children with steroid-resistant nephrotic syndrome

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Chapter 3: Steroid-sensitive nephrotic syndrome in children.

Project description: Not available

| S-EPMC4089737 | biostudies-literature

Gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with active idiopathic nephrotic syndrome (INS) and healthy controls (HC) [HC_vs_INS]

Project description:An autoimmune B cell origin for childhood idiopathic nephrotic syndrome (INS) is predicted based on the efficacy of rituximab (RTX) at maintaining long-term remission from proteinuria. Knowledge regarding the nature of the culprit B cell response is very limited. In particular, no transcriptomics work has been performed to evaluate the B cell response in INS. Using single-cell RNA-sequencing (scRNAseq) on peripheral blood mononuclear cells (PBMC) isolated from four affected children with active INS and four age/sex-matched health controls (HC), we demonstrate that a B cell transcriptional program poised for effector functions represents the major immune perturbation in the blood of children with active INS. We show that this nephrotic B cell signature is conferred by the engagement of memory B cells through an extrafollicular developmental route defined by expression of the interfollicular-homing gene GPR183 and the expansion of atypical B cells and marginal zone-like B cells. Moreover, we show that genes involved in APRIL signaling, which promotes extrafollicular antibody-secreting cell development, were substantially upregulated in B cells, monocytes, and dendritic cells from INS children. Collectively, our study provides evidence for an extrafollicular origin for humoral immunity in active INS.

2023-10-29 | GSE233275 | GEO

High resolution spatial trancrioptomics combined with deep learning-based image segmentation enables single-cell spatial profiling of archival FFPE kidney tissue from patients with idiopathic nephrotic syndrome

Project description:We have perfomed Visium HD spatial transcriptomics on archival FFPE kidney biopsies from patients with different manifistations of nephrotic syndrome, i.e., steriod sensitive, frequent relapsing and/or steroid dependent, and focal segmental glomerulosclerosis. Using a pre-trained deep learning model from StarDist to segment nuclei, we reconstructed single-nucleus level spatial trancriptomic datasets through custom binning of subcellular capture areas. We integrated the datasets from the different patients and indentified conserved cell types. Moreover, we identified patient specific transcriptomic differences in the podocyte cell population. This article demonstrates the usefullness of this approach to future studies of pathophysilogical mechanisms in idiopathic nephrotic syndrome.

2025-12-08 | GSE300895 | GEO

Population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome.

Project description:AimThe aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome.MethodsNon-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were receiving 2.5 mg kg(-1) levamisole (or placebo) orally once every other day. One hundred and thirty-six plasma samples were collected from 38 children from India and Europe and included in the analysis. A one compartment model described the data well.ResultsThe apparent clearance rate (CL/F) and distribution volume (V/F) were 44 l h(-1) 70 kg(-1) and 236 l 70 kg(-1) , respectively; estimated interindividual variability was 32-42%. In addition to allometric scaling of CL/F and V/F to body weight, we identified a significant proportional effect of age on CL/F (-10.1% per year). The pharmacokinetics parameters were not affected by gender, tablet strength or study centre. The median (interquartile range) maximum plasma concentration of levamisole was 438.3 (316.5-621.8) ng ml(-1) , and the median area under the concentration-time curve was 2847 (2267-3761) ng ml(-1) h. Median tmax and t½ values were 1.65 (1.32-2.0) h and 2.60 (2.06-3.65) h, respectively.ConclusionsHere, we present the first pharmacokinetic data regarding levamisole in children with steroid-sensitive nephrotic syndrome. The pharmacokinetic profile of levamisole in children was similar to findings reported in adults, although the elimination rate was slightly higher in children.

| S-EPMC4541972 | biostudies-literature

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