ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

Perturbations in Podocyte Transcriptome and Biological Pathways Induced by Injury Caused by FSGS Associated Circulating Factors

P. Rashmi1, T. Sigdel1, D. Rychkov1, I. Damm1, F. Vincenti1, C. Craik1, J. Reiser2, M. Sarwal1

1UCSF, San Francisco, CA, 2Rush University, Chicago, IL

Meeting: 2022 American Transplant Congress

Abstract number: 1301

Keywords: Autoimmunity, Gene expression, Kidney transplantation, Retransplantation

Topic: Basic Science » Basic Science » 16 - Biomarkers: -omics and Systems Biology

Session Information

Session Name: Biomarkers: -omics and Systems Biology

Session Type: Poster Abstract

Date: Monday, June 6, 2022

Session Time: 7:00pm-8:00pm

 Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: Focal segmental glomerulosclerosis (FSGS) remains a disease without specific therapy for primary disease and a high rate of recurrence after renal transplant. Circulating factors are implicated in the pathogenesis of FSGS but targeting them for therapy has remained elusive. We have previously described a panel of autoantibodies in sera from FSGS patients to predict the risk of recurrence after transplant with high accuracy. Furthermore, we showed interaction between two circulating factors- soluble urokinase-like plasminogen activator receptor (suPAR) and autoantibodies to CD40 in augmenting podocyte injury in vitro and in vivo. These studies suggested that anti uPAR and anti CD40 therapies may be effective in slowing down or reversing the renal injury leading to recurrence after transplant. The study presented here was conducted with two goals: 1) Validate the of role of CD40 and suPAR pathways in direct podocyte injury, and 2) Identify the molecules and pathways uniquely associated with CD40 and suPAR to find new markers and therapeutic candidates associated with podocyte injury in FSGS.

*Methods: Sera from three patients with biopsy proven FSGS and recurrence of FSGS after transplant was used to cause injury in immortalized human podocytes in culture. The efficacy of an anti uPAR antibody, 2G10 (developed by Dr. Charles Craik and described previously) or anti CD40 antibody (BMS 986090) was tested to reverse podocyte injury. For global transcriptomic profiling RNA was isolated from podocytes treated with anti CD40 antibody purified from patients with recurrence of FSGS, suPAR or both and subjected to whole Human Genome Microarray 4X44K (Agilent Technologies) for gene expression analysis.

*Results: Podocyte culture in the presence of sera from all three patients caused significant depolarization of stress fibers as determined by number of stress fiber positive cells (30%, 59% and 49% reduction with respected to untreated podocytes respectively), a hallmark of podocyte injury. Culture of podocytes with patient sera in the presence of anti CD40 antibody or 2G10 antibody (1ug/mL) against uPAR rescued stress fibers. CD40Ab caused upregulation of inflammatory genes involved in the regulation of type I interferon signaling pathway, cytokine-mediated signaling pathway and endothelial cell migration. Combined administration of patient derived CD40Ab and suPAR resulted in a primary response to suPAR with activation of genes involved in megakaryocyte differentiation. However, the addition of CD40Ab caused additional changes that are associated with integrin signaling.

*Conclusions: This study provides a proof of concept that inhibition of uPAR and CD40 signaling in podocytes can be an effective treatment strategy for recurrence of FSGS and potential abrogation of FSGS disease and renal allograft salvage.

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Rashmi P, Sigdel T, Rychkov D, Damm I, Vincenti F, Craik C, Reiser J, Sarwal M. Perturbations in Podocyte Transcriptome and Biological Pathways Induced by Injury Caused by FSGS Associated Circulating Factors [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/perturbations-in-podocyte-transcriptome-and-biological-pathways-induced-by-injury-caused-by-fsgs-associated-circulating-factors/. Accessed May 9, 2025.

« Back to 2022 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2025 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences