Mining the Human Urine Proteome for Monitoring Renal Transplant Injury
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE75693 | GEO | 2017/08/22
SECONDARY ACCESSION(S): PRJNA305092
REPOSITORIES: GEO
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Project description:Kidney transplant injury processes are associated with molecular changes in renal tissue, primarily related to immune cell activation and infiltration. How these processes are reflected by molecular alterations in circulating immune cells is poorly understood. We performed RNA-sequencing on 384 biobanked blood samples from four transplant centers, taken at time of a kidney allograft biopsy, selected for their phenotype (acute T cell- and antibody-mediated rejection, polyomavirus-associated nephropathy, and control). We performed differential expression analysis and pathway analysis per phenotype. In peripheral blood, differentially expressed genes in rejection vs. no rejection samples demonstrated upregulation of glucocorticoid receptor and NOD-like receptor signaling pathways. Pathways enriched in antibody-mediated rejection were strongly immune-specific, whereas pathways enriched in T cell-mediated rejection were less immune related. Differentially expressed genes in polyoma viremia and polyomavirus-associated nephropathy were similar and demonstrated upregulation of mitochondrial dysfunction and interferon signaling pathways. Our results highlight the immune activation pathways in peripheral blood leukocytes at time of antibody-mediated rejection and polyomavirus nephropathy and provide a framework for future therapeutic interventions.
2022-05-06 | GSE175718 | GEO
Project description:Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) has been shown to have anti-inflammatory effects such as decreased growth factors and cytokines in animal models, this effect however, has not been investigated in kidney transplant recipients. We aimed to study the effect of ACEI or ARB treatment on intragraft gene expression profiles of transplant kidney biopsies using microarrays. Both groups had similar demographic characteristics in terms of age, race, sex, type of transplant, previous history of transplantation or acute rejection, panel reactive antibody levels, and immunosuppressive treatment. There were no differences in acute and chronic Banff allograft injury scores between the 2 Groups. Intragraft gene expression profiles of ACEI or ARB treated Group 2 biopsies showed decreased gene transcripts of interferon-gamma and rejection-associated transcripts (GRIT) and constitutive macrophage-associated transcripts (CMAT) compared to Group 1 biopsies. There were no statistically significant differences in expression of cytotoxic T cell (CAT), regulatory T cell (TREG), B-cell (BAT), natural killer cell (NKAT), or endothelial cell-associated transcripts (ENDAT) between the 2 Groups. Our data suggest that exposure to ACEI or ARB was associated with down-regulation of GRIT and CMAT. This anti-inflammatory effect of ACEI or ARB treatment could be an additional benefit in kidney transplant recipients. We identified 29 near normal biopsies with chronic sum allograft injury score (ct+ci+cv) ⤠3 for gene expression profiling comparing 2 groups; Group 1 (n=16), patients with no exposure of ACEI or ARB treatment and Group 2 patients (n=13) with exposure to ACEI or ARB at least 6 months prior to kidney biopsy. Biopsies with a diagnosis of acute or chronic rejection, recurrent or de novo glomerular disease, or polyoma nephropathy were excluded.
2016-06-10 | E-GEOD-83095 | biostudies-arrayexpress
Project description:The study comprises various components: Samples TD: We aims to screen out different gene expression profile in donor biopsies after revascularization , We aims to predict renal allograft dysfunction early after transplantation. Samples AR, ATN, Tx: We aim to screen out different gene expression profile in acute rejection on the kidney. We aim to screen out different gene expression profile in acute tubular necrosis on the kidney. Results from the various study components can help to diagnose renal allograft dysfunction with different causes by distinct gene expression profile. Keywords: acute rejection, acute tubular necrosis, donor biopsies, renal allograft dysfunction
2011-02-02 | GSE26578 | GEO
Project description:The Australian Chronic Allograft Dysfunction (AUSCAD) study is an ongoing single centre cohort study at Westmead hospital in Australia. In this section of the study, we aimed to identify biomarkers for allograft rejection in kidney transplant recipients, 3-months after their transplant. Our study recruited 123 patients, each having protocol renal allograft biopsies taken 3-months post transplantation.
2024-04-05 | GSE261892 | GEO
Project description:Kidney transplantation is the treatment of choice for patients with end-stage chronic kidney disease (ESKD). Despite the usefulness of transplantation as replacement therapy, long-term graft survival represents a major challenge for transplant immunology. Although nowadays there has been an advance in understanding immunological mechanisms mediating rejection, and the improvement of immunomodulation therapies, there are still underlying molecular processes marking an important variability among patients, and presumably influencing allograft rejection. With our analysis we explored differences in gene expression by Next Generation Sequencing implementing RNA-Seq in biopsies, blood and urine from kidney transplant patients with acute and chronic rejection. For this, we performed an intra-outcome analysis simultaneously in acute and chronic rejection, with which we sought: 1. To identify differences in gene expression between peripheral blood vs renal tissue and peripheral blood vs urine in acute rejection and chronic rejection; 2. To identify the level of agreement in gene expression between renal tissue and urine in acute rejection and chronic rejection and 3. To identify genes and biological processes associated with acute rejection and chronic rejection that could be potentially detected in blood, and simultaneously in urine and biopsy in acute rejection and in chronic rejection.
2023-12-31 | GSE242302 | GEO
Project description:CONTEXT Slowly progressive chronic tubulo-interstitial damage jeopardizes long-term renal allograft survival. Both immune and non-immune mechanisms are thought to contribute, but the most promising targets for timely intervention have not been identified. OBJECTIVE In the current study we seek to determine the driving force behind progressive histological damage of renal allografts, without the interference of donor pathology, delayed graft function and acute graft rejection. DESIGN We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. PATIENTS Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection. RESULTS In this highly cross-validated study, we demonstrate the significant association of established, ongoing and future chronic histological damage with regulation of adaptive immune gene expression (T-cell and B-cell transcript sets) and innate immune response gene expression (dendritic cell, NK-cell, mast cell and granulocyte transcripts). We demonstrate the ability of gene expression analysis to perform as a quantitative marker for ongoing inflammation with a wide dynamic range: from subtle subhistological inflammation prior to development of chronic damage, over moderate subclinical inflammation associated with chronic histological damage, to marked inflammation of Banff-grade acute T-cell mediated rejection. CONCLUSION Progressive chronic histological damage after kidney transplantation is associated with significant regulation of both innate and adaptive immune responses, months before the histological lesions appear. This study therefore corroborates the hypothesis that quantitative inflammation below the diagnostic threshold of classic T-cell or antibody-mediated rejection is associated with early subclinical stages of progressive renal allograft damage. We used microarrays to examine whole genome expression profiles in renal allograft protocol biopsies, and analyzed the correlation between gene expression and the histological appearance over time. The gene expression profiles in these protocol biopsies were then compared with gene expression of biopsies with acute T-cell mediated rejection. Human renal allograft biopsies (N=120) were included: 96 rejection-free protocol biopsies and 24 biopsies with T-cell mediated acute rejection.
2011-12-10 | E-GEOD-25902 | biostudies-arrayexpress
Project description:In the present work, we have used whole genome expression profiling of peripheral blood samples from 51 patients with biopsy-proven acute kidney transplant rejection and 24 patients with excellent function and biopsy-proven normal transplant histology. The results demonstrate that there are 1738 probesets on the Affymetrix HG-U133 Plus 2.0 GeneChip representing 1472 unique genes which are differentially expressed in the peripheral blood during an acute kidney transplant rejection. By ranking these results we have identified minimal sets of 50 to 150 probesets with predictive classification accuracies for AR of greater than 90% established with several different prediction tools including DLDA and PAM. We have demonstrated that a subset of peripheral blood gene expression signatures can also diagnose four different subtypes of AR (Banff Borderline, IA, IB and IIA) and the top 100 ranked classifiers have greater than 89% predictive accuracy. Finally, we have demonstrated that there are gene signatures for early and late AR defined as less than or greater than one year post-transplant with greater than 86% predictive accuracies. We also confirmed that there are 439 time-independent gene classifiers for AR. Based on these results, we conclude that peripheral blood gene expression profiling can be used to diagnose AR at any time in the first 5 years post-transplant in the setting of acute kidney transplant dysfunction not caused by BK nephropathy, other infections, drug-induced nephrotoxicity or ureteral obstruction. Keywords: kidney transplantation, peripheral blood, DNA microarrays, acute kidney rejection, biomarkers Microarray profiles of peripheral blood from 51 biopsy-proven acute kidney rejection (AR) and 24 well-functioning kidney transplants were randomized and compared using class comparisons, network and biological function analyses.
2014-03-01 | E-GEOD-15296 | biostudies-arrayexpress
Project description:Specific early diagnosis of renal allograft rejection is gaining importance in the current trend to minimize and individualize immunosuppression. Gene expression analyses could contribute significantly by defining “molecular Banff” signatures. Several previous studies have applied transcriptomics to distinguish different classes of kidney biopsies. However, the heterogeneity of microarray platforms, clinical samples and data analysis methods complicates the identification of robust signatures for the different types and grades of rejection. To address these issues, a comparative meta-analysis was performed across five different microarray datasets of heterogeneous sample collections from two published clinical datasets and three own datasets including biopsies for clinical indications, protocol biopsies, as well as comparative samples from non-human primates (NHP). This work identified conserved gene expression signatures that can differentiate groups with different histopathological findings in both human and NHP, regardless of the technical platform used. The marker panels comprise genes that clearly support the biological changes known to be involved in allograft rejection. A characteristic dynamic expression change of genes associated with immune and kidney functions was observed across samples with different grades of CAN. In addition, differences between human and NHP rejection were essentially limited to genes reflecting interstitial fibrosis progression. This data set here comprises a small validation batch of renal allograft biopsies for clinical indications plus control normal kidney samples from patients at Hôpital Tenon, Paris (second batch) that complements the first batch of 60 samples. We used microarrays to identify different gene expression signatures of renal allograft biopsies that can classify them according to different types of allograft rejection or CAN. Keywords: disease state analysis 4 renal allograft core biopsies for clinical indications with different histopathological diagnoses according to Banff'97 criteria and 2 normal kidney samples.
2009-02-24 | E-GEOD-9492 | biostudies-arrayexpress
Project description:Specific early diagnosis of renal allograft rejection is gaining importance in the current trend to minimize and individualize immunosuppression. Gene expression analyses could contribute significantly by defining âmolecular Banffâ signatures. Several previous studies have applied transcriptomics to distinguish different classes of kidney biopsies. However, the heterogeneity of microarray platforms, clinical samples and data analysis methods complicates the identification of robust signatures for the different types and grades of rejection. To address these issues, a comparative meta-analysis was performed across five different microarray datasets of heterogeneous sample collections from two published clinical datasets and three own datasets including biopsies for clinical indications, protocol biopsies, as well as comparative samples from non-human primates (NHP). This work identified conserved gene expression signatures that can differentiate groups with different histopathological findings in both human and NHP, regardless of the technical platform used. The marker panels comprise genes that clearly support the biological changes known to be involved in allograft rejection. A characteristic dynamic expression change of genes associated with immune and kidney functions was observed across samples with different grades of CAN. In addition, differences between human and NHP rejection were essentially limited to genes reflecting interstitial fibrosis progression. This data set comprises all renal allograft biopsies for clinical indications from patients at Hôpital Tenon, Paris (February 2003 until September 2004) and few respective patients from Hôpital Bicêtre, Paris, Hôpital Pellegrin, Bordeaux, and Hôpital Dupuytren, Limoges, plus control normal kidney samples from Hôpital Tenon, Paris, France (first batch). We used microarrays to identify different gene expression signatures of renal allograft biopsies that can classify them according to different types of allograft rejection or CAN. Experiment Overall Design: 47 renal allograft core biopsies for clinical indications with different histopathological diagnoses according to BANFF'97 criteria, and 13 normal kidney samples as controls.
2009-02-28 | E-GEOD-9489 | biostudies-arrayexpress
Project description:The data set contains 67 array (lymphochip cDNA array), published in N Engl J Med 2003 Jul 10;349(2):125-38. PMID: 12853585. TITLE: Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. BACKGROUND: The causes and clinical course of acute rejection vary, and it is not possible to predict graft outcome reliably on the basis of available clinical, pathological, and genetic markers. We hypothesized that previously unrecognized molecular heterogeneity might underlie some of the variability in the clinical course of acute renal allograft rejection and in its response to treatment. METHODS: We used DNA microarrays in a systematic study of gene-expression patterns in biopsy samples from normal and dysfunctional renal allografts. A combination of exploratory and supervised bioinformatic methods was used to analyze these profiles. : We found consistent differences among the gene-expression patterns associated with acute rejection, nephrotoxic effects of drugs, chronic allograft nephropathy, and normal kidneys. The gene-expression patterns associated with acute rejection suggested at least three possible distinct subtypes of acute rejection that, although indistinguishable by light microscopy, were marked by differences in immune activation and cellular proliferation. Since the gene-expression patterns pointed to substantial variation in the composition of immune infiltrates, we used immunohistochemical staining to define these subtypes further. This analysis revealed a striking association between dense CD20+ B-cell infiltrates and both clinical glucocorticoid resistance (P=0.01) and graft loss (P<0.001). CONCLUSIONS: Systematic analysis of gene-expression patterns provides a window on the biology and pathogenesis of renal allograft rejection. Biopsy samples from patients with acute rejection that are indistinguishable on conventional histologic analysis reveal extensive differences in gene expression, which are associated with differences in immunologic and cellular features and clinical course. The presence of dense clusters of B cells in a biopsy sample was strongly associated with severe graft rejection, suggesting a pivotal role of infiltrating B cells in acute rejection. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: normal vs disease Keywords: disease_state_design Using regression correlation
2003-07-01 | E-GEOD-343 | biostudies-arrayexpress