Transcripts associated with chronic lung allograft dysfunction in transbronchial biopsies of lung transplants
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ABSTRACT:
PROVIDER: PRJNA795148 | ENA |
REPOSITORIES: ENA
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Project description:Transplanted lungs suffer worse outcomes than other organ transplants with many developing chronic lung allograft dysfunction (CLAD), diagnosed by physiologic changes. Histology of transbronchial biopsies (TBB) yields little insight, and the molecular basis of CLAD is not defined. We hypothesized that gene expression in TBBs would reveal the nature of CLAD and distinguish CLAD from changes due simply to time posttransplant. Time was associated with increased expression of inflammation genes e.g. CD1E and immunoglobulins. After correcting for time, CLAD manifested not as inflammation but as parenchymal response-to-wounding, with increased expression of genes such as HIF1A, SERPINE2, and IGF1 that are increased in many injury and disease states and cancers, associated with development, angiogenesis, and epithelial response-to-wounding in pathway analysis. Fibrillar collagen genes were increased in CLAD, indicating matrix changes, and normal transcripts were decreased – dedifferentiation. Gene-based classifiers predicted CLAD with AUC 0.70 (no time-correction) and 0.87 (time-corrected). CLAD-related gene sets and classifiers were strongly prognostic for graft failure and correlated with CLAD stage. Thus, in TBBs molecular changes indicate that CLAD primarily reflects severe parenchymal injury-induced changes and dedifferentiation.
2022-01-09 | GSE193150 | 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 chronic allograft dysfunction in kidney transplant recipients. Our study recruited 136 patients, each having protocol renal allograft biopsies taken pre transplantation.
2024-04-05 | GSE261240 | 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 transplants that develop dysfunction or proteinuria after one year post transplant are at considerable risk for progression to renal failure. Identifying the molecules associated with graft failure could potentially lead to interventions that would slow the progression of organ failure. We analyzed the relationship between gene expression in late biopsies for cause in human kidney transplants and subsequent graft loss, and assessed the predictive value of gene expression. We evaluated the performance of these genes in an independent , and in a population of early biopsies that have a very low risk of subsequent graft failure.
2010-05-24 | GSE21374 | GEO
Project description:Diagnosing lung transplant rejection currently depends on histologic assessment of transbronchial biopsies (TBB) with limited reproducibility and considerable risk of complications. Mucosal biopsies are safer but not histologically interpretable. Microarray-based diagnostic systems for TBBs and other transplants suggest such systems could assess mucosal biopsies as well.
2019-11-19 | GSE125004 | GEO
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 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 Samples AR1-AR17: This study has been accomplished with 17 patients of acute rejection on the kidney.Technical replicates: 2 replicates Samples ATN1-ATN5: This study has been accomplished with 5 patients of acute tubular necrosis on the kidney. Technical replicates: 2 replicates Samples Tx1-Tx14: This study has been accomplished with 14 patients of stable renal function on the kidney.Tecnical replicates:2 replicates(except Tx12) Samples TD1-TD12: This study has been accomplished with 12 patients of donor tissue with stable function early after transplantation on the kidney.Technical replicates: 2 replicates Samples TD13-TD21: This study has been accomplished with 9 patients of donor tissue with renal dysfunction early after transplantation on the kidney.Technical replicates: 2 replicates
2011-02-02 | E-GEOD-26578 | biostudies-arrayexpress
Project description:Chronic lung allograft dysfunction (CLAD) limits the long term survival after lung transplantation. CLAD is diagnosed late on the decline in lung function, when any immuno-intervention is ineffective. Identification of early forerunners of CLAD is therefore essential to prevent the progression of the disease before irreversible damages to the allograft. We used large-scale gene expression profiling of whole blood cells to identify early biomarkers of Bronchiolitis Obliterans Syndrome (BOS), the main form of CLAD. Microarray experiments performed from 80 patients (40 stable (STA) and 40 BOS) identify 47 genes differentially expressed between STA and BOS recipients. An independent set of patients (13 STA, 11 BOS) was then used for external validation by qPCR. POU Class 2 Associating Factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A) and B-cell lymphocyte kinase (BLK) genes were identified and validated as predictive markers of BOS more than 6 months before diagnosis with AUCs of 0.83, 0.77 and 0.78 respectively. These genes allow stratifying upon CLAD risk (log-rank test p<0.01) and could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.
2018-02-23 | GSE94557 | GEO
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 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. Keywords: disease state analysis
2009-02-24 | GSE9489 | GEO
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
2009-02-24 | GSE9492 | GEO