Microarray analysis of peripheral blood mononuclear cells (PBMCs) from IgA nephropathy patients, membranous nephropathy patients and healthy controls.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE73953 | GEO | 2016/04/22
SECONDARY ACCESSION(S): PRJNA298582
REPOSITORIES: GEO
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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: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.
2014-10-30 | GSE44974 | GEO
Project description:Background and objectives The activated complement profile in IgA nephropathy (IgAN) is still unclear. Our study investigated the profile of urinary complements in IgAN patients and their correlations with clinical and pathological characteristics. Methods Urinary protein abundance was detected by liquid chromatography-tandem mass spectrometry (LC‒MS/MS) in 50 IgAN, 50 membranous nephropathy (MN), and 68 healthy controls (HCs). Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify differentially expressed proteins in IgAN patients. Compared to HC and MN, differentially expressed complement proteins were screened in IgAN patients, and their correlations with laboratory or pathological parameters were analyzed. Then, 7 complement components were validated by enzyme-linked immunosorbent assay (ELISA) in the urine samples of 45 IgAN patients. Results There were 786 differentially expressed proteins between IgAN and HC. KEGG analysis showed that differentia
2022-11-28 | PXD038451 |
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 |
Project description:we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification.
2022-02-15 | PXD020288 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE35487: Expression data from human with IgA nephropathy (IgAN) [HG-U133A] GSE35488: Expression data from human with IgA nephropathy (IgAN) [HG-U133A_ENTREZG_10] Refer to individual Series
2012-02-02 | E-GEOD-35489 | biostudies-arrayexpress
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. total of 35 IgAN patients and 35 healthy blood donors (HBD) were included in this study. Illumina microarray technology was used to evaluate global differences in gene expression between monocytes isolated from IgAN patients and HBD. Bioinformatic analysis was performed with GenomeStudio and Genespring software. The connectivity between genes was evaluated using Ingenuity Pathway Analysis. Aberrantly expressed genes and pathways were then validated on an independent set of patients with RT-PCR western blot and flow cytometric analysis.
2015-03-30 | E-GEOD-58539 | biostudies-arrayexpress
Project description:The histologic diagnosis of idiopathic IgA Nephopathy (IgAN) is based o renal lesions scores. Aim of our study was to identify specific gene expression changes that characterize active renal lesions that may be more responsive to immunosuppressive therapy than chronic lesions. Total RNA was extracted from archival FFPE renal tissue samples of 55 IgAN patients, 31 non-IgAN patients. IgAN patients were accurately stratified based on the LUMPED classifications. Genome-wide gene expression profiles were generated and Oneway ANOVA with tukeyHSD post hoc testing was used to identify specific transcripts associated with active and chronic renal lesions in IgAN. RT-PCR was used to validate selected transcripts. Immunohistochemistry (IHC) was used to evaluate specific protein expression in biopsy specimens. Bioinfomatic analysis identified 183 genes with a Fold Change > 1.5 exclusively modulated in IgAN biopsies with active lesions and 162 genes with Fold Change > 1.5 exclusively modulated in IgAN biopsies with chronic lesions. These genes belonged to renal cellular damage and immune system regulatory pathways. To establish the validity of gene expression determined by microarray analysis, we performed RT-PCR on genes that were putatively involved in generating active and chronic lesions that may be involved in activating local inflammatory response and contributing to renal damage. Validated transcripts were also confirmed at protein level with IHC on kidney biopsy specimens. Transcriptomics on FFPE renal biopsies integrates histomorphologic renal lesions. Our study identifies specific gene expression changes involved in active and chronic lesions at the time of renal biopsy. This novel information may be used for personalized therapy through a system pharmacology approach to identify targeted molecules able to revert aberrant expression networks characterizing active and chronic lesions.
2020-06-02 | GSE115857 | GEO
Project description:IgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The disease is characterized by galactose deficient IgA (gd-IgA) in the circulation forming immune complexes. The complexes are deposited in the glomerular mesangium leading to inflammation and loss of renal function, but the pathophysiology of the disease is still not fully understood. Using an integrated global transcriptomic and proteomic profiling approach we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsies from patients with IgAN. The influence of galactose deficient IgA (gd-IgA) on mesangial cells was investigated by proteomic profiling. By utilizing the previous published literature curated glomerular cell type-specific genes, we found that mesangial cells and their positive standard genes play a more dominant role in IgAN comparing to the podocyte standard genes. Additionally, the patient clinical parameters (serum creatinine values and estimated glomerular filtration rate - eGFR) significantly correlate with z-scores derived from expression profile of mesangial cell positive standard genes. 22 common pathways were identified both from in vivo microarray data and in vitro mesangial cell mass spectrometry data and the main part was inflammatory pathways. The correlation between clinical data and mesangial standard genes allows for a better understanding of the onset of IgAN. The genes, proteins and their corresponding pathways identified in this paper give us novel insights into the pathophysiological mechanisms leading to progression of IgAN. RNA from glomerular compartment was extracted and processed for hybridization on Affymetrix microarrays. This dataset is part of the TransQST collection.
2017-07-03 | E-GEOD-93798 | biostudies-arrayexpress
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