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Gene expression-based, chronic active T cell-mediated rejection (CA TCMR)

ABSTRACT: Gene expression-based, chronic active T cell-mediated rejection (CA TCMR)

PROVIDER: PRJNA704388 | ENA |

REPOSITORIES: ENA

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Gene expression-based, chronic active T cell-mediated rejection (CA TCMR)

Project description:Expression profiling of a total of 1305 genes in 25 CA TCMR cases

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Transcriptomics of Chronic Active Antibody-Mediated Rejection of Human Kidney Allografts and Identification of Intragraft Overexpression of Natural Kill Cell Cytotoxicity Gene Set

Project description:The enigmatic natural killer (NK) cells mediate spontaneous cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity via cell surface Fc receptors. The dual functionality of NK cells may enable their participation in chronic active antibody-mediated rejection (CA-ABMR), wherein evidence for complement activation is inconsistent. We RNA sequenced 57 human kidney allograft biopsies to determine whether NK cell cytotoxicity pathway gene set enrichment is an attribute of CA-ABMR. Among the 15,910 intragraft-expressed genes, 60 were uniquely overexpressed in CA-ABMR compared to active antibody-mediated rejection (active-ABMR) or acute T cell-mediated rejection (TCMR), versus no rejection (NR) biopsies. Cell type annotation showed enrichment for T cells and NK cells, and molecular pathways related to T cells and NK cells in CA-ABMR versus active-ABMR biopsies. NK cell cytotoxicity gene set enrichment in CA-ABMR than in ABMR biopsies, but not in TCMR, was confirmed by gene set variation analysis. Cellular deconvolution analysis divulged a higher proportion of NK cells in CA-ABMR compared to active-ABMR, but not in TCMR; immunohistochemistry of 138 consecutive clinically indicated allograft biopsies validated a higher proportion of CD56+ NK cells in CA-ABMR. Principal component analysis of deconvolved immune cell transcriptomes separated CA-ABMR and TCMR from active-ABMR and NR biopsies. NK cell cytotoxicity pathway gene set was found to be enriched in rejection compared to no rejection biopsies in two publicly available kidney allograft microarray datasets. Altogether, CA-ABMR is exemplified by the overexpression of the NK cell pathway, and, surprisingly, compared to active-ABMR, is exemplified by key gene sets that are similar to TCMR.

2024-02-14 | GSE232825 | GEO

Histologic and molecular patterns in responders and non-responders with chronic-active antibody mediated rejection

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.

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Project description:Histologic and molecular patterns in responders and non-responders with chronic-active antibody mediated rejection

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Transciptomic signature of chronic antibody-mediated kidney rejection traited by extracorporeal photopheresis

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.

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Identification of new immunomarkers of active antibody-mediated rejection through glomerular proteome analysis in kidney transplantation

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2022-04-04 | PXD021852 | Pride

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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.

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Project description:Transplant glomerulopathy (TGP) is frequently found in the setting of chronic antibody mediated rejection along with microvascular inflammation (MVI) (peritubular capillaritis+glomerulitis score > 1) and/or positive c4d staining. We assessed the molecular profiles of TGP in the absence of microvascular inflammation and C4d staining as compared to TGP with positive MVI and/or C4d. Gene expression profiles of TGP in the absence of microvascular inflammation and C4d lack molecular features of antibody-mediated rejection but suggest chronic cellular rejection.

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Single-cell Transcriptome Analysis of Chronic Antibody-mediated Rejection after Renal Transplantation

Project description:Single-cell Transcriptome Analysis of Chronic Antibody-mediated Rejection after Renal Transplantation

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A novel model for chronic rejection in vascularized composite allotransplantation identifies CXCL9-11 as potential biomarkers

Project description:Global mRNA expression profiling of transplanted rat hindlimbs (muscle and skin) were collected using Agilent rat whole genome array (Agilent-028282 Whole Rat Genome Microarray 4x44K v3). Hind limb transplantation between Fischer344 (donor) and Lewis (recipient) rats were performed. Isogenic transplantations served as controls. Administration of irregular immunosuppression induced chronic rejection. At the endpoint (post-operativ day 100), hind limbs presented clinicial, histomorphological and genetic changes, known to be highly suspicious for chronic rejection.

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