ABSTRACT: The most common founder pathogenic variant c.868G>A (p.Val290Met) in the NPHS2 gene in a representative ADULT Czech cohort with Focal Segmental Glomerulosclerosis (FSGS) is associated with a milder disease and its underdiagnosis in childhood.
Project description:Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are patterns of kidney injury observed in the filtering units of the kidney known as glomeruli. From the NURTuRE cohort of individuals with nephrotic syndrome (NS), we performed laser microdissection and mass spectrometry analysis of kidney biopsy samples to identify proteomic patterns of disease. 56 individuals with idiopathic NS segregated by histological pattern (37 MCD and 19 FSGS) across three age groups: early childhood (0-6 years), late childhood (6-18 years) and adult (>18 years). We identified global differences in glomerular cell and extracellular matrix composition related to both histological pattern and age.
Project description:To search for biomarkers to differentiate Adult-Onset Steroid Sensitive focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Compared the profiles of glomerular transcriptomes between patients with FSGS and patients with MCD using microarray analysis. This dataset is part of the TransQST collection.
Project description:Transcriptome comparison of glomeruli from kidneys with focal segmental glomerulosclerosis (FSGS) and glomeruli from the unaffected portion of tumor nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.
Project description:Transcriptome comparison of tubular tissues from kidneys with focal segmental glomerulosclerosis (FSGS) and tubular tissues from the unaffected portion of tumor nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.
Project description:Transcriptome comparison of tubulointerstitial tissues from kidneys with focal segmental glomerulosclerosis (FSGS) and tubulointerstitial tissues from the unaffected portion of surgical nephrectomies. High-density Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used for the gene expression analysis.
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).
Project description:Focal segmental glomerulosclerosis (FSGS) is a leading cause of end stage renal disease and remains without specific treatment. To identify novel actors involved in the progression of FSGS, we used an experimental model of nephroangiosclerosis with FSGS in rats and performed a differential transcriptomic analysis. Among the genes that were several-fold upregulated in glomeruli, was Isthmin-1 (ISM), an ‘unknown’ to the kidney gene. The objective of the present study was to find if and what role plays ISM to renal pathophysiology.
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.
