Homo sapiens
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PROVIDER: PRJNA144251 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The ability to identify a robust means for both pediatric and adult liver transplant recipients for minimization and weaning of immunosuppression is greatly needed. We analyzed 298 samples from pediatric (n=83) and published adult (n=57) liver transplant recipients, and the public available cell or tissue specific samples (n=158). Biomarkers were first identified from the integration of the cross-platform analysis of Stanford pediatric and adult studies and validated in independent samples from UCLA on microarray. Furthermore, Q-PCR was performed for targets validation and delivers a robust diagnostic assay of predicting potential liver tolerance after liver transplantation. Thirteen unique genes were identified (FDR<5%) using nearest shrunken centroid classification methods as a minimum gene set to cross-validate and predict Stanford pediatric tolerance samples with 1misclassification, 5 misclassification for adult samples, and 100% sensitivity and 83% specificity for an independent UCLA pediatric samples in microarray platform. These subset of tolerant specific genes are highly expressed CD56+ natural killer cells (p=0.03). Furthermore, the subset can be narrowed down to 3 key genes with combined ROC=0.988 for the liver tolerance prediction from Q-PCR verification and 64% MIS and STA were predicted as tolerance with the >90% prediction probability. Specific peripheral transcriptional programs can be identified in operational tolerance in pediatric recipients of liver allografts, distinct from those previously identified in adult operationally tolerant liver recipients, and may provide a means to non-invasively monitor patients in a serial manner for immunosuppression minimization. These genes are highly expressed in specific peripheral blood lymphocyte subsets, and their coordinated may support the maintenance of operational tolerance in children, following liver transplantation. Two centers data was included, which are 41 samples from Stanford as the training set and 44 samples from UCLA as the test set. 26 samples from Stanford and 15 samples from UCLA were used in microarray Agilent whole human genome microarray
2012-02-01 | E-GEOD-30886 | biostudies-arrayexpress
Project description:The ability to identify a robust means for both pediatric and adult liver transplant recipients for minimization and weaning of immunosuppression is greatly needed. We analyzed 298 samples from pediatric (n=83) and published adult (n=57) liver transplant recipients, and the public available cell or tissue specific samples (n=158). Biomarkers were first identified from the integration of the cross-platform analysis of Stanford pediatric and adult studies and validated in independent samples from UCLA on microarray. Furthermore, Q-PCR was performed for targets validation and delivers a robust diagnostic assay of predicting potential liver tolerance after liver transplantation. Thirteen unique genes were identified (FDR<5%) using nearest shrunken centroid classification methods as a minimum gene set to cross-validate and predict Stanford pediatric tolerance samples with 1misclassification, 5 misclassification for adult samples, and 100% sensitivity and 83% specificity for an independent UCLA pediatric samples in microarray platform. These subset of tolerant specific genes are highly expressed CD56+ natural killer cells (p=0.03). Furthermore, the subset can be narrowed down to 3 key genes with combined ROC=0.988 for the liver tolerance prediction from Q-PCR verification and 64% MIS and STA were predicted as tolerance with the >90% prediction probability. Specific peripheral transcriptional programs can be identified in operational tolerance in pediatric recipients of liver allografts, distinct from those previously identified in adult operationally tolerant liver recipients, and may provide a means to non-invasively monitor patients in a serial manner for immunosuppression minimization. These genes are highly expressed in specific peripheral blood lymphocyte subsets, and their coordinated may support the maintenance of operational tolerance in children, following liver transplantation.
2012-02-01 | GSE30886 | GEO
Project description:The achievement of a drug-free operational tolerance for renal transplanted patients is a major goal in organ transplantation. Previous gene expression profiling in peripheral blood mononuclear cells (PBMC) identified genes associated with operational tolerance. The identification of a common pattern of B cell-related genes associated with tolerance encourage us to analyze gene expression in purified B cell from operationally tolerant patients (TOL=10) compared to renal transplanted patients with stable graft function (STA=12) under immunosuppression and also compared to healthy volunteers (HV=10) who have no immunosuppressive treatment and no graft. Microarray analyses exhibited an absence of gene signature associated with tolerance in purified B cell compared to STA or HV. These results suggest that the B cell signatures observed in PBMC may be due to an increase number of total B cells rather than specific B cell characteristics in operationally tolerant patients. This dataset represents gene expression profiling of purified B cells from 10 renal transplanted patients with operational tolerance (TOL), 12 renal transplanted patients with stable graft function under immunosuppression (STA) and 10 healthy volunteers (HV).
2015-08-01 | E-GEOD-39899 | biostudies-arrayexpress
Project description:The achievement of a drug-free operational tolerance for renal transplanted patients is a major goal in organ transplantation. Previous gene expression profiling in peripheral blood mononuclear cells (PBMC) identified genes associated with operational tolerance. The identification of a common pattern of B cell-related genes associated with tolerance encourage us to analyze gene expression in purified B cell from operationally tolerant patients (TOL=10) compared to renal transplanted patients with stable graft function (STA=12) under immunosuppression and also compared to healthy volunteers (HV=10) who have no immunosuppressive treatment and no graft. Microarray analyses exhibited an absence of gene signature associated with tolerance in purified B cell compared to STA or HV. These results suggest that the B cell signatures observed in PBMC may be due to an increase number of total B cells rather than specific B cell characteristics in operationally tolerant patients.
2015-08-01 | GSE39899 | GEO
Project description:Transplant recipients spontaneously accepting their grafts in the absence of immunosuppression demonstrate the feasibility of attaining allograft tolerance in humans. Previous studies have identified blood transcriptional and cell phenotypic markers specific for either liver or kidney tolerant recipients, but the two settings have not been directly compared yet employing the same platforms. To identify potential similarities in immune parameters between recipients tolerant to different organs, we analyzed blood samples from tolerant and non-tolerant liver and kidney recipients employing whole genome expression microarrays. Tolerant and non-tolerant liver and kidney recipients differed in their peripheral blood expression patterns, but no significant overlap was observed between the two datasets. This was confirmed at the functional level by employing gene set enrichment analysis.The lack of obvious similarities in immune parameters associated with liver and kidney tolerant recipients implies the involvement of different mechanisms in the two settings and argues against the existence of a common immunological constant of spontaneous operational tolerance in clinical transplantation. The complete database comprised the expression measurements of 54,675 genes for liver and kidney trasplant inmunotolerance groups (n=12 for each group).A group of 12 samples from Healthy volunteer are included.
2012-01-01 | E-GEOD-22707 | biostudies-arrayexpress
Project description:Transplant recipients spontaneously accepting their grafts in the absence of immunosuppression demonstrate the feasibility of attaining allograft tolerance in humans. Previous studies have identified blood transcriptional and cell phenotypic markers specific for either liver or kidney tolerant recipients, but the two settings have not been directly compared yet employing the same platforms. To identify potential similarities in immune parameters between recipients tolerant to different organs, we analyzed blood samples from tolerant and non-tolerant liver and kidney recipients employing whole genome expression microarrays. Tolerant and non-tolerant liver and kidney recipients differed in their peripheral blood expression patterns, but no significant overlap was observed between the two datasets. This was confirmed at the functional level by employing gene set enrichment analysis.The lack of obvious similarities in immune parameters associated with liver and kidney tolerant recipients implies the involvement of different mechanisms in the two settings and argues against the existence of a common immunological constant of spontaneous operational tolerance in clinical transplantation.
2012-01-01 | GSE22707 | GEO
Project description:Multiparameter Immune Profiling of Operational Tolerance in Liver Transplantation
| PRJNA105697 | ENA
Project description:Immune tolerance is involved physiologically in pregnancy and disrupted in autoimmunity, organ rejection, and graft-versus-host disease (GvHD). In transplantation setting, operational tolerance has been inferred in patients who develop tolerance without a need for immunosuppressants. However, mechanisms underlying operational tolerance in Humans are poorly understood. Using two cohorts of patients who underwent an allo-HSCT from HLA-identical siblings, we used multi-omics approach to decipher immune landscape associated with tolerance in recipients and their related donors. We analyzed two cohorts of patients, one monocentric from Saint Louis hospital (cohort 1, n=41) and one multicenric from the national Cryostem consortium biological collection (cohort 2, n=69). We proceed to deep immunophenotyping of peripheral blood mononuclear cell using mass cytometry, RNA sequencing analysis and metabolomics profiling of plasma in both recipients and related donors. The aim of this study is to determine the evolution of immune landscape after allogeneic HSCT by comparison with healthy donors, and to identify specific biological mechanism associated with immune tolerance in patients.
2021-09-01 | GSE150735 | GEO
Project description:Operational tolerance after solid organ transplantation is defined as stable graft acceptance without immunosuppression while maintaining normal immunocompetence against immunological insults. However, it is not clear yet which cellular and molecular pathways are driving tolerance in these patients and how this state can be induced in order to improve graft survival. Several transcriptomic analysis have shown that transcription signatures in blood can reflect the immunological state associated with operational tolerance in kidney transplant. Nonetheless, epigenetic dynamics orchestrating these transcription signatures have not yet been studied. Here, we performed genome-wide analysis of DNA methylation of kidney transplant recipients with chronic rejection and operational tolerance. Our data showed that chronic rejection and operational tolerance recipients have differential DNA methylation in 2737 genes, indicating that each patient group has a specific epigenetic signature associated with transplant outcome. In addition, we observed that operational tolerance is associated with DNA demethylation in genes involved in immune function, including B cell activation (e.g. ST6GAL1, MS4A1 and MEF2C) and the Th17 differentiation program (e.g. LY9 and BATF), while in CR patients is mostly associated intracellular signaling and ubiquitination pathways. Finally, we used weighted gene co-expression network analysis (WGCNA) to select the more defining epigenetic changes associated with operational tolerance. By this method, we select 12 genomic regions specifically hypomethylated (HIVEP2, HOMER1, UTRN, PTPRO, SP100 and JAZF1) or hypermethylated (EMZ8, EZR-AS, WDR20, NADSYN1, TBCD and MED17) in tolerant patients. Analysis of these genes in stable transplant recipients with immunosuppression showed that these patients have a similar methylation signature to operational tolerance recipients. Overall, these results demonstrate that DNA methylation in blood can mirror the immune status associated with kidney transplant outcome and provides a starting point for understanding the epigenetic mechanisms associated with operational tolerance.
2021-08-12 | GSE156359 | GEO
Project description:Survival of solid organ grafts depends on life-long immunosuppression, which results in increased rates of infection and malignancy. Induction of tolerance to allografts would represent the optimal solution for controlling both chronic rejection (CR) and side effects of immunosuppression. Although spontaneous ‘‘operational tolerance’’ can occur in human kidney transplantation, the lack of noninvasive peripheral blood biological markers of this rare phenomenon precludes the identification of potentially tolerant patients in whom immunosuppression could be tapered as well as the development of new tolerance inducing strategies. Here, the potential of high throughput microarray technology to decipher complex pathologies allowed us to study the peripheral blood specific gene expression profile and corresponding EASE molecular pathways associated to operational tolerance in a cohort of human kidney graft recipients. In comparison with patients with CR, tolerant patients displayed a set of 343 differentially expressed genes, mainly immune and defense genes, in their peripheral blood mononuclear cells (PBMC), of which 223 were also different from healthy volunteers. Using the expression pattern of these 343 genes, we were able to classify correctly >80% of the patients in a cross-validation experiment and classified correctly all of the samples over time. Collectively, this study identifies a unique PBMC gene signature associated with human operational tolerance in kidney transplantation. 250 samples were analyzed, replicates included: some patients from the TOL and CR groups were sampled twice with an interval between the two different time points of at least 16 months (mean 25.8 months, range 16–31 months). All the samples were analyzed in duplicate or quadruplicate. 1. TOL (n = 21). patients with stable graft function (blood creatinemia<150 mmol/L, proteinuria<1 g/24 h) for at least 1 year (mean 6.4 years,range 1.6–17.2 years) after complete interruption of immunosuppressive therapy. 2. STA (n = 190). Patients with stable kidney graft function under immunosuppressive therapy. 3. CR (n = 31). Patients having a progressive degradation of their renal function (blood creatinemia ≥150 mmol/L, proteinuria ≥1 g/24 h). CR was diagnosed on a graft biopsy according to the updated Banff criteria. CR was defined by histological signs of chronic allograft arteriopathy (arterial intimal fibrosis with mononuclear cell infiltration) and/or transplant glomerulopathy with glomerular double contours. 4. HV (n = 8). Subjects having normal blood formulae and no infectious or other concomitant pathology for at least 6 months before the study.
2017-02-09 | GSE47755 | GEO