Similar Datasets
Project description:The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated. Molecular signatures characterizing CNIT samples were identified. The recognized CNIT gene signature was most common in patients with decreased graft function and histological evidence of IF/TA.
2014-06-01 | GSE53605 | GEO
Project description:Chronic lung allograft dysfunction (CLAD) is the leading cause of death in lung transplant recipients. CLAD is characterized clinically by a persistent decline in pulmonary function and histologically by the development of airway centered fibrosis known as bronchiolitis obliterans. We performed single-cell sequencing and spatial transcriptomic analysis of explanted tissues from human lung recipients with CLAD and donor control lungs.
2023-03-21 | GSE224210 | GEO
Project description:The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated. Molecular signatures characterizing CNIT samples were identified. The recognized CNIT gene signature was most common in patients with decreased graft function and histological evidence of IF/TA. To test CNIT contribution to CAD progression, kidney biopsies from transplant recipients with histological diagnosis of CNIT (n=14), acute rejection (ACR, n=13), and CAD with IF/TA (n=10), including 18 Normal allografts, were analyzed using gene expression microarrays.
2014-06-01 | E-GEOD-53605 | biostudies-arrayexpress
Project description:Purpose: Chronic allograft dysfunction (CAD) remains a major obstacle in kidney transplantation. However, the molecular pathogenesis of human CAD is unknown. Herein, we tested the hypothesis that single nuclei transcriptomics of human kidney allograft fibrosis will reveal diverse cell types, deconvolve complex fibrosis-driving pathways, and provide deeper insights into the progression of kidney allograft dysfunction.
2023-03-06 | GSE195718 | GEO
Project description:Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value=38±34%%; negative predictive value=73±30%, c-statistic=0.59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and 0.58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e. those with a relatively normal 1-year biopsy and eGFR >40) remains difficult.
2021-08-31 | GSE181757 | GEO
Project description:We investigated blood miRNAs as potential non-invasive biomarkers in kidney transplantation as part of the BIOMARGIN consortium (ClinicalTrials.gov, number NCT02832661). Blood samples were collected at time of the 717 renal allograft biopsies, in four European transplant centers. Profiling of mIR transcriptomes was performed in a multistage discovery-to-validation study. Antibody-mediated rejection (ABMR) is the most common cause of allograft failure after kidney transplantation. The revised Banff 2017 classification defines ABMR as conditions in which histologic evidence of acute and chronic injury is associated with evidence of current/recent antibody interaction with vascular endothelium and serologic evidence of donor-specific antibodies (DSA) to human leukocyte antigen (HLA) or non-HLA antigens
2021-05-31 | E-MTAB-9595 | biostudies-arrayexpress
Project description:To assess the preclinical utility and functional mechanism of intraperitoneal anti-CX3CL1 mAb therapy in the skin and lung fibrosis, sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) model mice were analyzed by RNA-sequencing assays.
2024-05-03 | GSE227285 | GEO
Project description:We study the global gene expression profiles of TGP patients with or without graft loss to determine if a clinical and/or gene expression profile can predict allograft survival. Transplant glomerulopathy (TGP) carries a poor prognosis and is associated with decreased allograft survival. In a large series of kidney transplant recipients, graft loss was observed in 38% of TGP patients at 5 years compared to 5% in patients without TGP. Among patients with TGP, predictors of poor outcome included C4d deposition in the peritubular capillaries, higher serum creatinine and proteinuria at diagnosis, the severity of interstitial fibrosis, and GBM duplication (higher Banff ‘chronic glomerulopathy [cg]’ score), and the presence of DSA. However, the importance of microvascular inflammation determined by peritubular capillaritis (ptc) and glomerulitis (g) scores and the strength of DSA has not been explored thoroughly. We have recently reported the intragraft gene expression profiles of TGP patients, with or without DSA. However, the association between gene expression profiles of biopsies and the allograft survival has not been investigated. In this study, in addition to known clinical and demographic factors associated with poor outcomes in TGP, we specifically aimed to investigate if intragraft gene expression profiles by microarrays, microvascular inflammation scores, and the strength of DSA determined by mean fluorescence intensity (MFI) values could predict allograft loss in TGP patients.
2014-06-18 | GSE58601 | GEO
Project description:Acute rejection episodes trigger chronic renal allograft vasculopathy. Numerous leukocytes, predominantly monocytes, accumulate in graft blood vessels during reversible acute rejection preceding chronic rejection of rat kidneys. We speculate that they contribute to transplant vasculopathy and set out to characterize them. Allogeneic renal transplantation was performed in the Fischer 344 to Lewis rat strain combination, Lewis isografts served as controls. Leukocytes were harvested by intensive perfusion of graft blood vessels and subjected to flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling.
2010-09-24 | GSE18266 | GEO
Project description:Chronic rejection after organ transplantation manifests as immunosuppressant-resistant graft vascular remodeling and fibrosis, which remains the dominant driver of mortality after the first year of heart transplantation. Single-cell RNAseq analysis of MHCII-mismatched heart transplants developing chronic rejection identified graft IL-33 as a stimulator of tissue repair pathways in infiltrating myeloid cells and regulatory T cells (Tregs). Using IL-33-deficient donor mice, it was revealed that graft fibroblast-derived IL-33 potently induced Amphiregulin (Areg) expression by recipient Treg. Areg is an epidermal growth factor secreted by multiple immune cells to shape immunomodulation and tissue repair. In particular, Areg is proposed to play a major role in Treg-mediated muscle, epithelium, and nerve repair. Assessing recipient mice with Treg-specific deletion of Areg demonstrated that this pathway surprisingly contributes to chronic rejection. Specifically, heart transplants from recipients with Areg-deficient Tregs exhibited less vasculopathy and vessel-associated fibrotic niches infiltrated by recipient T cells. Mechanistically, we show that Areg does not impact Treg suppressive function, but that IL-33 mediated Treg-secretion of Areg increases fibroblast proliferation and migration. In total, these studies identify how a dysregulated repair response involving interactions between IL-33+ fibroblasts in the allograft and recipient Treg contributes to the progression of chronic rejection.
2024-12-02 | GSE235871 | GEO