ALTERED MONOCYTE GENE EXPRESSION AND EXPANSION OF CD14+CD16+ SUBSET IN IgA NEPHROPATHY PATIENTS
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Sharon Cox
PROVIDER: E-GEOD-58539 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The basic defect of IgA nephropathy (IgAN) lies within peripheral blood mononuclear cells rather than local kidney abnormalities. Previously we showed an altered gene expression in monocytes compared to B and T cells isolated from IgAN patients (Kidney Int, 2010), thus our aim here was to study this subset more closely at genome-wide level.
2015-03-30 | GSE58539 | GEO
Project description:The hallmark of IgA nephropathy (IgAN) is gross hematuria (GH) coinciding with or immediately following an upper respiratory or gastrointestinal tract infection and can represent the disease triggering event. Therefore, a whole genomic screening of IgAN patients during the GH was done to clarify the link between mucosal encountered antigens and the occurrence of glomerular hematuria. The modulated genes during GH show a clear involvement of the interferon signalling, antigen presenting pathway, and the immuno-proteasome. The gene characterizing cytotoxic effector lymphocytes (CX3CR1) implicated in vascular endothelial damage, was found up-regulated at both mRNA and protein level. In vitro antigenic stimulation of PBMCs on an independent set of IgAN patients and healthy blood donors (HBS) demonstrated that patients upregulate specifically CX3CR1 in an enhanced and dose dependant manner, while an expected down-regulation occurred in HBD. This enhanced activation occurred in both patients characterized by recurrent GH and by permanent microscopic hematuria (MH). We then analyzed glomerular fractalkine (FKN) expression, since this ligand is involved in the vascular gateway for CX3CR1+ cells towards the inflamed tissues. A significantly higher FKN expression on the capillary vessels and podocytes was found in recurrent GH patients compared to permanent MH, suggesting a predisposition for cytotoxic cell extravasation in recurrent GH patients. Taken together, our findings demonstrate, for the first time, a defect in antigen handling in PBMCs of IgAN patients with a specific up-regulation of CX3CR1. Furthermore, the constitutive up regulation of glomerular FKN, suggests an involvement of the CX3CR1-FKN axis in the exacerbation of GH. Gene expression profile comparison 3 IgAN patients at two different clinical time points, the first sample during the gross hematuria episode and the second during the remission phase of the disease characterized by microscopic hematuria
2012-03-29 | E-GEOD-27676 | biostudies-arrayexpress
Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN) RNA from tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix HG-U133A microarrays.
2012-02-02 | E-GEOD-35487 | biostudies-arrayexpress
Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN) RNA from tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix HG-U133A microarrays.
2012-02-02 | E-GEOD-35488 | biostudies-arrayexpress
Project description:Immunoglobulin A Nephropathy (IgAN) is a complex multifactorial disease whose genetic bases remain unknown. Distinct linkage and genome-wide association studies in both familial and sporadic IgAN suggest that there is a strong genetic component in IgAN. In this context, an intriguing role could be ascribed to copy number variants (CNVs) that have been recognized as an important source of genetic variation in humans. Here, we performed a whole-genome screening of CNVs in IgAN patients, their healthy relatives and healthy subjects (HS). A total of 217 individuals consisting of 51 IgAN cases and 166 healthy relatives were included in the initial screening. The high-throughput analysis of structural genetic variations, to find concordant aberrations across classes of samples, identified 178 IgAN-specific aberrations, specifically 114 loss and 64 gain. Several CNVs overlapped with regions evidenced by previous genome-wide genetic studies. Moreover, we found that IgAN patients characterized by deteriorated renal function carried low copy numbers of a CNV in chromosome 3 (chr3_loss:52031010-52260722). This CNV contained the TLR9 gene whose expression significantly correlated with the loss aberration in patients with progressive renal damage. Conversely, IgAN patients with normal renal function had no chr3_loss:52031010-52260722 and the TLR9 mRNA was expressed at the same level as in HS, still maintaining a strong correlation with the CNV. In conclusion, here we performed the first genome-wide CNV study in IgAN identifying some structural variants specific to IgAN patients and providing a collection of new candidate genes and loci that could help to dissect the complex genomic setting of the disease. Moreover, we identified a specific CNV, spanning the TLR9 gene, which could explain the disease severity in IgAN patients. To perform a genome-wide CNV study in IgAN identifying some structural variants specific to IgAN patients and providing a collection of new candidate genes and loci that could help to dissect the complex genomic setting of the disease.
2014-10-30 | E-GEOD-44974 | biostudies-arrayexpress
Project description:This study identifies immune transcript signatures that may predict IgAV nephritis in skin biopsies and distinguish IgA-IRGN from IgAN and IgAV in kidney biopsies
2023-08-08 | GSE220100 | GEO
Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN)
2012-02-02 | GSE35488 | GEO
Project description:Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 albumin-regulated genes differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n=25) could be distinguished from those of control subjects (n=6) based solely upon the expression of these 231 albumin-regulated genes. The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that the all forms of primary glomerulonephritis (n=33) can be distinguished from controls (n=21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis. We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgA nephropathy (IgAN)
2012-02-02 | GSE35487 | GEO
Project description:The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.
2021-04-02 | GSE171314 | GEO
Project description:IgA nephropathy (IgAN) is a heterogeneous disease, which poses a series of challenges to accurate diagnosis and personalized therapy. Here, we present a systematic quantitative kidney tissue proteome atlas across 19 tumor-adjacent normal kidney tissues, 12 membranous nephropathy (MN) samples and 59 biopsies from IgAN patients. Consensus sub-clustering of proteome profiles divided IgAN into three subtypes (IgAN-C1, C2 and C3). Compared to IgAN-C2, the IgAN-C1, and C3 subtypes had a different regulating mechanism and exhibited higher levels of complement activation, more severe mitochondrial injury, and more significant extracellular matrix accumulation. Additionally, IgAN-C1 and C3 had worse clinical outcomes than C2 (30% serum creatinine increase as the end point, P<0.01). Overall, the novel proteomic prognostic subtyping of IgAN could help us understand the heterogeneity of IgAN and improve clinical outcomes.
2022-03-22 | PXD032710 | iProX