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Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis[Tubulointerstitial]

ABSTRACT: Expression data from human with hypertensive nephropathy (HT) We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with HT

ORGANISM(S): Homo sapiens

PROVIDER: GSE37455 | GEO | 2012/12/10

SECONDARY ACCESSION(S): PRJNA160203

REPOSITORIES: GEO

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Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis[Tubulointerstitial]

Project description:Expression data from human with hypertensive nephropathy (HT) We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with HT RNA from glomeruli and tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix microarrays.

2012-12-10 | E-GEOD-37455 | biostudies-arrayexpress

Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis [Glomeruli]

2012-12-10 | GSE37460 | GEO

Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis [Glomeruli]

Project description:Expression data from human with IgA nephropathy (IgAN) and hypertensive nephropathy (HT) We used microarrays to analyze the transcriptome of microdissected renal biopsies from patients with IgAN and HT RNA from glomeruli and tubulointerstitial compartments was extracted and processed for hybridization on Affymetrix microarrays.

2012-12-10 | E-GEOD-37460 | biostudies-arrayexpress

Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis.

Project description:Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus. Therapeutic studies in mouse LN models do not always predict outcomes of human therapeutic trials, raising concerns about the human relevance of these preclinical models. In this study, we used an unbiased transcriptional network approach to define, in molecular terms, similarities and differences among three lupus models and human LN. Genome-wide gene-expression networks were generated using natural language processing and automated promoter analysis and compared across species via suboptimal graph matching. The three murine models and human LN share both common and unique features. The 20 commonly shared network nodes reflect the key pathologic processes of immune cell infiltration/activation, endothelial cell activation/injury, and tissue remodeling/fibrosis, with macrophage/dendritic cell activation as a dominant cross-species shared transcriptional pathway. The unique nodes reflect differences in numbers and types of infiltrating cells and degree of remodeling among the three mouse strains. To define mononuclear phagocyte-derived pathways in human LN, gene sets activated in isolated NZB/W renal mononuclear cells were compared with human LN kidney profiles. A tissue compartment-specific macrophage-activation pattern was seen, with NF-κB1 and PPARγ as major regulatory nodes in the tubulointerstitial and glomerular networks, respectively. Our study defines which pathologic processes in murine models of LN recapitulate the key transcriptional processes active in human LN and suggests that there are functional differences between mononuclear phagocytes infiltrating different renal microenvironments.

| S-EPMC3392438 | biostudies-literature

Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2012-12-10 | E-GEOD-37463 | biostudies-arrayexpress

Cross-species transcriptional network analysis defines shared inflammatory responses in murine and human lupus nephritis

Project description:This SuperSeries is composed of the SubSeries listed below.

2012-12-10 | GSE37463 | GEO

NCAM1: A Novel Autoantigen in Membranous Lupus Nephritis

Project description:Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. Unlike phospholipase A2 receptor or thrombospondin type 1 domain containing 7A-associated membranous nephropathy, where known antibodies can be detected within sera by indirect immunofluorescence and/or enzyme-linked immunosorbent assay, it is not possible to monitor disease activity in membranous lupus nephritis where the target autoantigens are mostly unknown. Determination of the target autoantigen has diagnostic significance, informs prognosis, and allows for non-invasive monitoring of disease activity in serum. We utilized mass spectrometry for antigen discovery of laser capture microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue IgG immunoprecipitation studies from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1-associated membranous neuropathy was 5.7% of cases of membranous lupus nephritis. NCAM1 co-localizes with IgG within glomerular immune deposits. Additionally, serum from NCAM1 patients showed reactivity to NCAM1 recombinant protein. The presence of anti-NCAM1 antibodies in sera could allow for non-invasive monitoring of the disease. We propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.

2020-10-19 | PXD021123 | Pride

Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring.

Project description:In lupus nephritis, glomerular injury correlates poorly with progression to renal failure. While the tubulointerstitium is also commonly involved, the importance of such involvement is not well defined. Therefore, we developed a simple method to assess the prognostic utility of measuring tubulointerstitial inflammation (TI).Sixty-eight systemic lupus erythematosus patients with lupus nephritis were enrolled. Tubulointerstitial lymphocytic infiltrates were quantitated both by anti-CD45 antibody staining and standard histochemical staining. Followup data were obtained and survival analysis was carried out to determine which histologic features were predictive of subsequent renal failure.By CD45 staining, TI was a common pathologic finding, with 72% of biopsies having moderate or severe involvement. The extent of TI correlated with serum creatinine, but not with double-stranded DNA antibodies, serum C3, or glomerular inflammation. TI severity, but not glomerular injury, identified patients at greater risk for renal failure (P = 0.02). A high National Institutes of Health (NIH) chronicity index also identified patients at risk for renal failure. However, when the glomerular and tubulointerstitial subcomponents of the NIH chronicity index were separated in a bivariate model, only tubulointerstitial chronicity provided prognostic information (hazard ratio [HR] 2.2, 95% confidence interval [95% CI] 1.3-3.6; P = 0.002 versus HR 1.0, 95% CI 0.7-1.5; P = 0.97 for glomerular chronicity).TI identifies lupus nephritis patients at greatest risk for progression to renal failure. The immunologic mechanisms underlying TI may provide novel targets for therapeutic intervention.

| S-EPMC3106120 | biostudies-other

RNA-seq profiling of tubulointerstitial tissue reveals a potential therapeutic role of dual anti-phosphatase 1 in kidney diseases

Project description:We profiled manually microdissected tubulointerstitial tissue from 43 IgA nephropathy, 3 diabetes mellitus nephropathy, 3 focal segmental glomerulosclerosis, 3 lupus nephritis, 4 membranous nephropathy, and 9 minimal change disease biopsy cores and 22 nephrectomy controls by RNA sequencing. The 3 outliers which were not included in our main analysis were also uploaded in this database.

2022-05-02 | GSE175759 | GEO

Case Report: Predominant Tubulointerstitial Lupus Nephritis or the Combination With IgG4-Related Disease?

Project description:Isolated or dominant tubulointerstitial lupus nephritis is rare. Here, we reported a 67-year-old man diagnosed with systemic lupus erythematosus (SLE) based on clinical and laboratory criteria, who was showing impaired renal function and non-nephrotic range proteinuria in the past 2 years. Renal biopsy showed almost normal glomeruli, but the tubulointerstitium showed "storiform" pattern with interstitial infiltration of IgG3 predominant plasma cells. Immunofluorescence showed linear and granular staining of IgG and C1q along TBM and interstitium. He started on medium dose of oral steroids and mycophenolate mofetil, which were gradually tapered. As a result, his renal function improved over a few days. Now, he continued on low dose steroids and mycophenolate mofetil with no evidence of relapse.

| S-EPMC8273166 | biostudies-literature

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