Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA245423 | ENA |
REPOSITORIES: ENA
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Project description:Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause of early and accelerated graft loss. Immuneadsorption can alleviate renal dysfunction and suggests that circulating antibodies (Ab) are likely implicated in disease pathogenesis. To evaluate pathogenic Ab in rFSGS, we processed 141 unique serum samples from patients with and without primary rFSGS (n=64) and 34 non-FSGS control, transplanted at five (US and EU) hospitals. 9000 antigens were screened in pre-transplant sera by protein arrays and 10 Ab targeting glomerular antigens were selected for ELISA validation. A panel of 7 Ab (CD40, PTPRO, CGB-5, FAS, P2RY11, SNRPB2 and APOL2) could predict post-transplant FSGS recurrence with 92% accuracy. Pre-transplant elevation of anti-CD40 Ab levels alone had a substantial impact (78% accuracy) on the identification of rFSGS risk after transplantation. Epitope mapping of CD40 with customized peptide arrays and rFSGS sera demonstrated altered immunogenicity of the extracellular CD40 domain in rFSGS. Immunohistochemistry of CD40 demonstrated a differential expression of these antigens in FSGS compared to non-FSGS. Anti-CD40 Ab purified from rFSGS patients were uniquely pathogenic in human podocyte cultures; injection of these Ab resulted in heightened proteinuria, independently and in combination with suPAR in a rodent model, abrogated by injection of monoclonal Ab to CD40. In conclusion, a panel of 7 Ab can identify primary FSGS patients at high risk of recurrence prior to transplantation, allowing for customized therapies and improved patient selection for transplant. Intra-renal CD40 is an important axis of disease pathogenesis, and human trials of anti-CD40 therapies are warranted to evaluate their efficacy in preventing rFSGS and improving graft survival. The purpose of the study was to identify potential auto-Abs associated with rFSGS. We used a discovery set of pre-transplant sera from 20 unique patients with biopsy confirmed diagnosis of primary FSGS as their cause of ESRD, of which 10 had progressed to rFSGS within the first post-transplant year and 10 did not have recurrence of proteinuria or histological disease after transplantation (nrFSGS).
2014-11-04 | E-GEOD-57099 | biostudies-arrayexpress
Project description:Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause of early and accelerated graft loss. Immuneadsorption can alleviate renal dysfunction and suggests that circulating antibodies (Ab) are likely implicated in disease pathogenesis. To evaluate pathogenic Ab in rFSGS, we processed 141 unique serum samples from patients with and without primary rFSGS (n=64) and 34 non-FSGS control, transplanted at five (US and EU) hospitals. 9000 antigens were screened in pre-transplant sera by protein arrays and 10 Ab targeting glomerular antigens were selected for ELISA validation. A panel of 7 Ab (CD40, PTPRO, CGB-5, FAS, P2RY11, SNRPB2 and APOL2) could predict post-transplant FSGS recurrence with 92% accuracy. Pre-transplant elevation of anti-CD40 Ab levels alone had a substantial impact (78% accuracy) on the identification of rFSGS risk after transplantation. Epitope mapping of CD40 with customized peptide arrays and rFSGS sera demonstrated altered immunogenicity of the extracellular CD40 domain in rFSGS. Immunohistochemistry of CD40 demonstrated a differential expression of these antigens in FSGS compared to non-FSGS. Anti-CD40 Ab purified from rFSGS patients were uniquely pathogenic in human podocyte cultures; injection of these Ab resulted in heightened proteinuria, independently and in combination with suPAR in a rodent model, abrogated by injection of monoclonal Ab to CD40. In conclusion, a panel of 7 Ab can identify primary FSGS patients at high risk of recurrence prior to transplantation, allowing for customized therapies and improved patient selection for transplant. Intra-renal CD40 is an important axis of disease pathogenesis, and human trials of anti-CD40 therapies are warranted to evaluate their efficacy in preventing rFSGS and improving graft survival.
2014-11-04 | GSE57099 | GEO
Project description:Kidney transplantation is the preferred treatment for kidney failure, offering improved survival, quality of life and cost-effectiveness compared to dialysis. However, post-transplant management is challenging due to the limited lifespan of transplanted organs, often requiring repeat transplants. Current methods for monitoring post-transplant complications are invasive and have limitations. Therefore, there is an urgent need for novel non-invasive biomarkers. This study investigates the proteomic composition of full urine as a source of information to understand renal biology during the process of transplantation and to identify potential markers for outcome prediction. Urine samples were collected from donors (timepoint A) before transplantation and from recipients 4 weeks (timepoint B) and 1 year (timepoint C) after transplantation. Proteomic analysis was performed using mass spectrometry and label-free quantification. This study underscores the potential of non-invasive urine proteomics for identifying biological processes involved in the response of a kidney to transplantation and for enhancing post-transplant monitoring and outcome prediction.
2026-04-01 | PXD071468 | Pride
Project description:Kidney transplantation is the preferred treatment for kidney failure, offering improved survival, quality of life and cost-effectiveness compared to dialysis. However, post-transplant management is challenging due to the limited lifespan of transplanted organs, often requiring repeat transplants. Current methods for monitoring post-transplant complications are invasive and have limitations. Therefore, there is an urgent need for novel non-invasive biomarkers. This study investigates the proteomic composition of full urine as a source of information to understand renal biology during the process of transplantation and to identify potential markers for outcome prediction. Urine samples were collected from donors before transplantation and from recipients 4 weeks and 1 year after transplantation. Proteomic analysis was performed using mass spectrometry and label-free quantification. This study underscores the potential of non-invasive urine proteomics for identifying biological processes involved in the response of a kidney to transplantation and for enhancing post-transplant monitoring and outcome prediction.
2026-04-01 | PXD057361 | Pride
Project description:Background: Many patients with idiopathic focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but there is no consensus about the identity of CPFs in FSGS. We aimed to find proteins involved in the mechanism of action of the CPF(s) and/or potential biomarkers for the presence of CPF(s). Methods: Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s), or from (disease) controls. Podocyte proteomes were analyzed by mass spectrometry and differentially expressed proteins were validated using flow cytometry, RT-PCR, and immunofluorescence. Changes in podocyte granularity were examined using flow cytometry, electron microscopy imaging and BODIPY staining. Results: Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, which was related to disease state and capacity of plasma to induce granularity in podocytes. Elevated perilipin-2 levels were confirmed at protein and mRNA level. The granules observed in podocytes actually are lipid droplets. Importantly, increased perilipin-2 staining was also detected in glomeruli of the FSGS patients whose active disease plasmas induced lipid droplets in podocytes. Conclusions: Our study demonstrates that presumably CPF-containing plasma from FSGS patients alter podocyte lipid metabolism and increase perilipin-2 protein and lipid droplet accumulation. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism in the context of the pathogenesis of (recurrent) FSGS, which ultimately may result in novel leads for treatment.
2022-12-22 | PXD028536 | Pride
Project description:Introduction: Responses to allogeneic human leukocyte antigen (HLA) molecules limit the survival of transplanted organs. The changes in T-cell alloreactivity that contribute to this process, however, are not fully understood. We defined a set of donor reactive T-cell clones (DRTC) with the goal to elucidate signatures of kidney allograft rejection. Methods: DRTC were identified pretransplant using an anti-donor mixed lymphocyte reaction assay: CFSE-diluting CD4+ and CD8+ DRTC were flow-sorted, and the TCR sequences were identified using Adaptive Immunosequencing. DRTC were then tracked in post-transplant biopsies, blood, and urine samples in a cohort of kidney transplant recipients. Results: In patients with an abnormal biopsy, the majority of CD8+ DRTC found within the allograft were detected in the circulating pre-transplant repertoire. Circulating CD8+ DRTC were more abundant pre- and post-transplant in patients that received non-lymphodepletional induction and developed an abnormal biopsy when compared to stable patients. Additionally, DRTC were detected as early as two weeks post-transplant in the urine of some patients, with some of these clones subsequently identified in follow-up kidney biopsy samples. Discussion: The findings of our study add to our understanding of T-cell alloreactivity following kidney transplantation and provide evidence for the role of pre-defined alloreactive T-cells in the development of allograft rejection.
2025-02-10 | GSE288648 | GEO
Project description:This study explores these differences by comparing the proteomes of proximal tubules and serum from normoglycemic (NG), pre-transplant T2DM, and PTDM patients one-year post-kidney transplantation.
2025-05-26 | PXD054937 | Pride
Project description:This study explores these differences by comparing the proteomes of proximal tubules and serum from normoglycemic (NG), pre-transplant T2DM, and PTDM patients one-year post-kidney transplantation.
2025-05-26 | PXD054961 | Pride
Project description:Diabetes mellitus (DM) after transplantation remains a crucial clinical problem in kidney transplantation. To obtain insights into molecular mechanisms underlying the development of post-transplant diabetes mellitus (PTDM) and its early impact on glomerular structures, here we comparatively analyze the proteome of histologically normal appearing glomeruli from patients with PTDM from normoglycemic (NG) transplant recipients, and from recipients with pre-existing type 2 DM (PTDM)
2023-10-24 | PXD042188 | Pride
Project description:Minimal change disease and primary focal segmental glomerulosclerosis (FSGS) are common causes of nephrotic syndrome. Both diseases present with massive proteinuria and widespread foot process effacement on electron microscopy examination. On the other hand, secondary FSGS can also present with significant proteinuria, although the extent of foot process effacement can be variable. In this study, we performed laser microdissection of glomeruli followed by mass spectrometry to study podocyte proteins and compare the differences between the 3 diseases. Our study shows significant decrease in total spectral counts of nephrin, podocin, CD2-associated protein, alpha actinin 4, inverted formin 2 and dystroglycan 1 in all 3 diseases compared to time zero kidney transplant controls and membranous nephropathy biopsies (p <0.001). On the other hand, the decrease in the podocyte proteins in minimal change disease, primary FSGS and secondary FSGS was comparable and there was no significant difference. Surprisingly, there was no significant decrease in the podocyte proteins in membranous nephropathy compared to time zero kidney transplant control biopsies. In conclusion, our study shows significant decrease in major podocyte proteins in minimal change disease, primary and secondary FSGS, but not in time zero kidney transplant controls and in membranous nephropathy.
2025-12-29 | PXD057165 | Pride