Single-cell Transcriptome Analysis of Chronic Antibody-mediated Rejection after Renal Transplantation
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ABSTRACT:
PROVIDER: PRJNA786646 | ENA |
REPOSITORIES: ENA
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Project description:Renal transplantation is currently the most effective treatment for end-stage renal disease. However, chronic antibody-mediated rejection (cABMR) remains a serious obstacle for the long-term survival of patients with renal transplantation and a problem to be solved. At present, the role and mechanism underlying immune factors such as T- and B- cell subsets in cABMR after renal transplantation remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) of peripheral blood monocytes (PBMCs) from cABMR and control subjects was performed to define the transcriptomic landscape at single-cell resolution. A comprehensive scRNA-seq analysis was performed. The results indicated that most cell types in the cABMR patients exhibited an intense interferon response and release of proinflammatory cytokines. In addition, we found that the expression of MT-ND6, CXCL8, NFKBIA, NFKBIZ, and other genes were up-regulated in T- and B-cells and these genes were associated with pro-inflammatory response and immune regulation. GO and KEGG enrichment analyses indicated that the overexpressed genes in T- and B-cells were mainly enriched in inflammatory pathways, including the TNF, IL-17, and Toll-like receptor signaling pathways. Additionally, MAPK and NF-κB signaling pathways were also involved in the occurrence and development of cABMR. Trajectory analysis assembled the T-cell subsets into three differentiation paths with distinctive phenotypic and functional prog rams. CD8 effector T cells and γδ T cells showed three different differentiation trajectories, while CD8_MAI T cells and naive T cells primarily had two differentiation trajectories. Cell-cell interaction analysis revealed strong T/B cells and neutrophils activation in cABMR. Thus, the study offers new insight into pathogenesis and may have implications for the identification of novel therapeutic targets for cABMR.
2022-01-12 | GSE190329 | GEO
Project description:Endothelial, inflammatory, cellular, interferon gamma and calcineurin inhibitor related genes were analyzed in 10 therapy responders and 6 non responders in chronic active antibody mediated rejection (caABMR) in kidney transplantation.
2022-01-04 | GSE192552 | GEO
Project description:Background: The benefit of extracorporeal photopheresis on the course of kidney transplant rejection is unknown. The aim of our study was to investigate the variations in transcriptomics on graft biopsies when extracorporeal photopheresis was used to treat chronic humoral rejection after kidney transplantation. Methods: we retrospectively analyzed the mRNA expression of 770 genes of interest in graft biopsies performed before and after treatment. Eight patients received an average of 23 extracorporeal photopheresis sessions over 4 months between the two biopsies. Results: Transcriptomic analysis of the graft biopsies identified a significant (adjusted p-value< 0.05) increase in CAV1 mRNA in all patients and a significant decrease in CD19, IL21, PAX5, and SFTPA2 mRNAs in 7 of 8 patients. Conclusions: In patients treated with extracorporeal photopheresis for chronic humoral rejection after renal transplantation, omic analysis of repeated biopsies shows a reduction in fibrotic and inflammatory transcriptomic signatures.
2024-02-28 | GSE240778 | GEO
Project description:Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss, but its pathogenesis is unclear. In order to uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of circulating peripheral blood mononuclear cells and, separately, of CD4+ T lymphocytes isolated from CAMR patients compared to kidney transplant recipients with normal graft function and histology. In total peripheral lympho-monocytes, forty-five genes resulted differentially expressed between the two groups, most of them were up-regulated in CAMR and were involved in type I interferon signaling. In addition, in the same set of patients, 16 microRNAs resulted down-regulated in CAMR subjects compared to controls: 4 were predicted modulators of 6 mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signaling. To further confirm this hypothesis, we investigated the transcriptomic profiles of CD4+ T lymphocytes in an independent group of patients and we observed that the activation of type I interferon signaling was a specific hallmark of CAMR. In addition, in CAMR patients we detected a reduction of circulating BDCA2+ dendritic cells, the natural type I interferon- producing cells and their recruitment into the graft along with an increased expression of MXA, a type I interferon-induced protein, at tubulointerstitial and vascular level. In conclusion, our data suggest that type I interferon signaling may represent the molecular signature of CAMR. For microarray analysis, we studied 5 patients included into the control-group and 4 included into the study group. The control group was represented by renal transplant recipients undergoing protocol graft biopsies, with normal renal function and histology, in the absence of circulating anti-HLA antibodies. Study group patients showed clinical and histological evidence of CAMR according to Banff 2011 criteria.
2015-12-10 | E-GEOD-51676 | biostudies-arrayexpress
Project description:Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss, but its pathogenesis is unclear. In order to uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of circulating peripheral blood mononuclear cells and, separately, of CD4+ T lymphocytes isolated from CAMR patients compared to kidney transplant recipients with normal graft function and histology. In total peripheral lympho-monocytes, forty-five genes resulted differentially expressed between the two groups, most of them were up-regulated in CAMR and were involved in type I interferon signaling. In addition, in the same set of patients, 16 microRNAs resulted down-regulated in CAMR subjects compared to controls: 4 were predicted modulators of 6 mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signaling. To further confirm this hypothesis, we investigated the transcriptomic profiles of CD4+ T lymphocytes in an independent group of patients and we observed that the activation of type I interferon signaling was a specific hallmark of CAMR. In addition, in CAMR patients we detected a reduction of circulating BDCA2+ dendritic cells, the natural type I interferon- producing cells and their recruitment into the graft along with an increased expression of MXA, a type I interferon-induced protein, at tubulointerstitial and vascular level. In conclusion, our data suggest that type I interferon signaling may represent the molecular signature of CAMR. For microarray analysis, we studied 8 patients included into the control-group and 10 included into the study group. The control group was represented by renal transplant recipients undergoing protocol graft biopsies, with normal renal function and histology, in the absence of circulating anti-HLA antibodies. Study group patients showed clinical and histological evidence of CAMR according to Banff 2011 criteria.
2015-12-10 | E-GEOD-51675 | biostudies-arrayexpress
Project description:Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss, but its pathogenesis is unclear. In order to uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of circulating peripheral blood mononuclear cells and, separately, of CD4+ T lymphocytes isolated from CAMR patients compared to kidney transplant recipients with normal graft function and histology. In total peripheral lympho-monocytes, forty-five genes resulted differentially expressed between the two groups, most of them were up-regulated in CAMR and were involved in type I interferon signaling. In addition, in the same set of patients, 16 microRNAs resulted down-regulated in CAMR subjects compared to controls: 4 were predicted modulators of 6 mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signaling. To further confirm this hypothesis, we investigated the transcriptomic profiles of CD4+ T lymphocytes in an independent group of patients and we observed that the activation of type I interferon signaling was a specific hallmark of CAMR. In addition, in CAMR patients we detected a reduction of circulating BDCA2+ dendritic cells, the natural type I interferon- producing cells and their recruitment into the graft along with an increased expression of MXA, a type I interferon-induced protein, at tubulointerstitial and vascular level. In conclusion, our data suggest that type I interferon signaling may represent the molecular signature of CAMR. We performed microarray experiments in CD4+ T cells isolated from a small independent group of 5 patients included into the control-group and 5 included into the study group. The control group was represented by renal transplant recipients undergoing protocol graft biopsies, with normal renal function and histology, in the absence of circulating anti-HLA antibodies. Study group patients showed clinical and histological evidence of CAMR according to Banff 2011 criteria.
2015-12-10 | E-GEOD-64261 | biostudies-arrayexpress
Project description:Issues remain in the diagnosis of active antibody-mediated rejection (ABMR) in human kidney transplantation, as the hallmark criteria, the microcirculation inflammation scores and the C4d deposits, still lack reproducibility and sensitivity respectively. Using laser microdissection combined with mass spectrometry-based proteomics, this study presents the characterization of active antibody-mediated glomerular injuries, marked by evidences of leukocyte activation and migration, cellular stress through type I and II interferons and of microcirculation remodeling.
2022-04-04 | PXD021852 | Pride
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:We performed small RNA-Seq and compared expression levels of microRNAs of whole blood cells isolated from patients after kidney transplantation with stable graft function (SGF), antibody-mediated rejection (ABMR) and T cell-mediated rejection (TCMR).
2018-08-20 | GSE115816 | GEO
Project description:We performed total RNA-Seq and compared expression levels of genes of whole blood cells isolated from patients after kidney transplantation with stable graft function, antibody mediated- and t cell mediated graft rejection.
2018-10-04 | GSE120649 | GEO