Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular characterization of kidney compartments from serial biopsies to differentiate treatment responders from non-responders in lupus nephritis

ABSTRACT: The immune pathways that define treatment response and non-response in lupus nephritis (LN) are unknown. To characterize these intra-renal pathways, transcriptomic analysis of protocol kidney biopsies was done. Kidney biopsies were done at flare (Bx1) and after treatment (Bx2) in 58 LN patients and healthy controls (HC). Glomeruli and tubulointerstitium (TI) were isolated using laser microdissection. RNA was extracted and analyzed by nanostring. Transcript expression from clinical complete (CR), partial (PR) and non-responders (NR) were compared at Bx1 and Bx2 and to HC. Top transcripts that differentiate CR from NR were identified. Confocal microscopy and urine ELISA was done to evaluate the protein expression of top transcripts. At Bx1 cluster analysis determined that glomerular integrin, neutrophil, and chemokine/cytokine, and TI chemokine, T cell and leukocyte adhesion genes differentiated NR from CR. At Bx2, glomerular monocyte, extracellular matrix, and interferon, and TI interferon, complement, and T cell transcripts differentiated NR from CR. Protein analysis recapitulated top transcript findings. Urine C5a and FN1 differentiated NR from CR after treatment. Transcript analysis of serial kidney biopsies taken during the treatment of LN demonstrated how gene expression in the kidney changes with clinically successful and unsuccessful therapy. These insights into the molecular landscape of response and non-response may help better align LN management with the pathogenesis of kidney injury.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200306 | GEO | 2022/07/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Microarray profiles from glomerular compartment of kidney biopsies from adults screened for enrollment in the NEPTUNE cohort

Project description:Glomerular Transcriptome from kidney biopsies of adult patients screened for enrollment into NEPTUNE

2022-04-15 | GSE200828 | GEO

circRNA-sequencing

Project description:We aim to identify profiling of circRNAs in renal biopsies from lupus nephritis (LN) patients. In this study, seven frozen renal biopsies from patients with LN class IV were used for circRNA profiling by second generation of RNA sequencing. Three kidney tissue 5 cm far from renal tumors were used as normal control .

2020-12-16 | GSE108340 | GEO

Expression data from human with lupus nephritis (LN)

Project description:Nephritis (LN) is a serious manifestation of SLE. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these models. In this study we used an unbiased transcriptional network approach to define similarities and differences between three lupus models and human LN. Affymetrix-based expression profiles were analyzed using Genomatix Bibliosphere software and transcriptional networks were compared using the Tool for Approximate LargE graph matching (TALE). The 20 network hubs (nodes) shared between all three models and human LN reflect key pathologic processes, namely immune cell infiltration/activation, macrophage/dendritic cell activation, endothelial cell activation/injury and tissue remodeling/fibrosis. Each model also shares unique features with human LN. Pathway analysis of the TALE nodes highlighted macrophage/DC activation as a cross-species shared feature. To distinguish which genes and activation pathways might derive from mononuclear phagocytes in the human kidneys the gene expression profile of isolated NZB/W renal mononuclear cells was compared with human LN kidney profiles. Network analysis of the shared signature highlighted NFkappaB1 and PPARgamma as major hubs in the tubulointerstitial and glomerular networks respectively. Key nodes in the renal macrophage inflammatory response form the basis for further mechanistic and therapeutic studies. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with lupus nephritis (LN) RNA from glomeruli and tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix microarrays.

2012-06-27 | E-GEOD-32591 | biostudies-arrayexpress

The Molecular Phenotype of Lupus Nephritis Histological Lesions

Project description:Lupus nephritis (LN) is characterized by immune-complex deposition in kidney glomeruli and has been classified according to histological features, but has not been characterized on a molecular level. This study aimed to characterize the relationship between histological and molecular phenotypes in LN. Renal compartmental mRNA expression was measured in 54 kidney biopsy specimens from patients with LN and correlated to histological phenotypes. The top identified transcripts were compared to a separate longitudinal cohort of 36 patients with paired kidney biopsies obtained at the time of flare and at follow up. Unsupervised clustering based on mRNA abundance resulted in clear separation by renal compartment, but did not demonstrate a relationship with LN class based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, or the NIH activity and chronicity indices. A strong interferon gene signature was observed in both cohorts. FN1, SPP1, and LGALS-3 correlated with disease activity in both cohorts. The relationship between mRNA expression and ISN/RPS classification is modest. However, correlation of mRNA expression with individual histologic lesions identifies transcripts that change with resolution of disease flare, and provide insights into the molecular pathways potentially responsible for pathologic kidney lesions. Combining molecular and pathologic kidney biopsy phenotype may hold promise to better classify disease and identify actionable treatment targets.

2019-10-29 | GSE127797 | GEO

Expression data from human with lupus nephritis (LN)

2012-06-28 | GSE32591 | GEO

Expression data from kidney biopsies of liver disease patients

Project description:Glomerular abnormalities have been demonstrated in kidney biopsies of patient after orthotopic liver transplantation (OLT). We hypothesize that these changes exist prior to OLT and may play a role in the development of renal failure after OLT. We use gene expression microarrays to investigate the mechanism of kidney disease in patients listed for OLT. Gene expression profiles of biopsies of cirrhotic patients were compared with pre-implantation living donor biopsies. Glomerular abnormalities were seen in 92% of the biopsies, the most common being increase in mesangial matrix. Electron microscope showed effacement of podocytes (93%) and duplication (35%) and widening of glomerular basement membrane (45%). Gene Ontology analysis revealed significant up-regulation of genes implicated in immune response, including T-cell, leucocyte and platelet activation and differentiation. Pathogenesis-based transcripts analysis revealed significantly increased expression of cytotoxic T-cell, macrophage, B-cell, natural killer cell, and endothelial cell associated transcripts, indicating an ongoing inflammatory immune response.

2013-09-17 | GSE50892 | GEO

Shared molecular targets in the glomerular transcriptome from patients with nephrotic syndrome and ANCA-associated vasculitis

2018-05-17 | GSE108109 | GEO

Shared molecular targets in the glomerular transcriptome from patients with nephrotic syndrome and ANCA-associated vasculitis

Project description:Glomerular transcriptome from human kidney biopsies in Neptune and ERCB. A subset of samples profiled in this analysis were also profiled in Series GSE68127, and in GSE104066. Corresponding tubulointerstitial transcriptome data is submitted under GEO ID: GSE108113. RNA from the glomerular compartment was extracted and processed for hybridization on Affymetrix ST 2.1 microarrays, annotated using Human Entrez Gene ID custom CDF version 19. This dataset is part of the TransQST collection.

2018-05-17 | E-GEOD-108109 | biostudies-arrayexpress

Expression data from Human Kidney (HK) samples

Project description:Males are 50% more likely to develop end stage kidney failure compared to women. In this study we wanted to find out the molecular mechanism responsible for this increased risk. We collected kidney samples from patients with and without kidney disease and performed a comprehensive gene expression analysis in healthy and diseased male and female kidneys. Interestingly, the set of gender biased genes in healthy kidneys were different from those in diseased kidneys indicating not only baseline gene expression differences but also that the male and female kidney respond differently to disease condition. Our studies indicate that men and women with kidney problems might need to be treated differently. Keywords: Gender difference We collected 42 kidney samples from healthy living transplant donors, nephrectomies and from diagnostic kidney biopsies. Preliminary studies did not show significant gene expression differences in control kidneys based on the collection method (i.e. living kidney biopsy vs. unaffected portion of tumor nephrectomy). We grouped the tissue samples based on the histological readings of the kidney biopsies. Samples with evidence of glomerular and tubulointerstitial fibrosis were assigned into the diseased group. Characteristics of the research participants indicate diverse ethnic and disease groups and mild (StageIII) CKD. The tissue was microdissected into glomerular and tubulointerstitial fractions and expression arrays were performed separately.

2010-04-13 | E-GEOD-12682 | biostudies-arrayexpress

Transcription profiling of microdissected human transplant kidney biopsies obtained from five cadaveric and five matched live donors before transplantation

Project description:Recipients of live donor transplant kidneys (LIV) exhibit a significantly longer allograft half-life compared with cadaveric donor organs (CADs). The reasons are incompletely understood. Therefore this study sought to elucidate the genome-wide gene expression profiles in microdissected transplant kidney biopsies obtained from five cadaveric and five matched live donors before transplantation. cDNA microarrays were used to determine the transcripts in isolated glomeruli (G) and the tubulointerstitial (TI) compartment. Data were subjected to hierarchical clustering, maxT adjustment and a jackknife procedure to ensure robustness of reported findings; validation was performed by independent analysis of split biopsies and TaqMan-PCR. One hundred and thirteen sequences representing 62 unique genes (17 redundant features), and 34 ESTs separated G from TI. No difference in gene expression was found in G between LIV and CAD kidneys, but nine genes (two represented twice) and three ESTs were abundantly expressed in the CAD TI compared with LIV. The main biological function of these genes is counter regulation of oxidative stress. Promoter analysis of significant features suggested coregulated gene groups. These data suggest that CAD kidneys exhibit a distinctly different set of transcripts in the TI compartment but not in the G compartment when compared with LIV kidneys.

2005-11-09 | E-SMDB-3022 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data