Project description:C3 glomerulopathy (C3G), which encompasses C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation is limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression. We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and 6 DDD) who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The Nanostring 770 genes immune profiling panel was used for transcriptomic analysis. Disease recurrence was the primary outcome. During a median follow-up period of 37 (18, 56) months, C3G recurrence occurred in 16 (89%) of patients (11 with C3GN and 5 with DDD), at a median of 33 (13, 141) days post-transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence. The majority of patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played crucial role in detecting early, sub-clinical recurrence of C3GN and DDD, which showed significant overlapping features. To identify transcriptomic signals that may distinguish recurrent C3G, we utilized the 770 genes PanCancer Immune Profiling Panel in a discovery cohort of native kidney biopsies followed by a testing cohort of allograft biopsies. For the discovery cohort, we residual tissue from formalin-fixed paraffin-embedded samples (FFPE) was used from 18 native kidney biopsies with C3G (11 C3GN and 7 DDD) and 36 native biopsies with other glomerular diseases (GD controls: 15 IgA nephropathy, 14 membranous nephropathy, 7 diffuse podocytopathy). For the testing cohort, we ass essedresidual FFPE tissue was used from 13 index allograft biopsies with recurrent C3G (combining 10 from our study with enough residual tissue and 3 additional cases that were added to increase sample size) and 41 allograft glomerular disease (GD) controls. Since recurrent GD is overall more commonly encountered than de novo GD although the frequency of latter might be underestimated20, the GD controls were selected to roughly reflect this notion [15 de novo GD (5 membranous nephropathy, 6 immune complex-mediated glomerulonephritis not otherwise specified, 3 IgA nephropathy, 1 HCV-associated glomerulonephritis) and 26 recurrent GD (10 membranous nephropathy, 8 IgA nephropathy, 7 diffuse podocytopathy, 1 HCV-associated glomerulonephritis)].
Project description:Acute allograft rejection is a leading cause for the failure of organ allotransplantation. Identifying the genes involved in the rejection process provides clues to study the mechanisms, and to provide specific gene targets for monitoring, predicting and preventing acute allograft rejection. Using a mice model of skin acute allograft rejection and SAGE method, we analyzed gene expression in the CD4+ T cells of the mice, the cell type known to play critical roles in acute allograft rejection. Our study identifies 402 SAGE tags significantly different from these from the control. From these SAGE tags, we identified 91 increasingly and 85 decreasingly expressed genes, and many genes have not been linked with acute allograft rejection before. Functional classification of these genes shows that apoptosis, transcription regulation, cell growth and maintenance and signal transduction are among the most frequently changed functional groups. Our study provides a genome-wide view for the genes involving acute allograft rejection in the CD4+ T cells, and indicates that acute allograft rejection involves multiple genes in different functional categories. The genes identified from the study provide candidates for further studying the mechanisms and for monitoring, predicting and preventing acute allograft rejection.
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.
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.
Project description:Rat corneal allograft rejection models were established to investigate the effects and mechanisms of resveratrol on corneal allograft rejection after corneal transplantation.
Project description:Self-reactive antibodies cloned from B cells infiltrating in a human renal allograft were subjected to IP-mass spectrometry using nuclear lysates of HEp-2 cells.