Autoantibodies reactive with glomerular endothelial cells and podocytes in patients with membranous nephropathy

Vojtech Petr; Shrey Purohit; Felix Poppelaars; Brandon Renner; Jennifer Laskowski; Russell Whelan; Liudmila Kulik; Jessica Kendrick; Ashley Frazer-Abel; Diana Jalal; Barbara Marcolin; Isabelle Schmelzer; Hanna Debiec; Pierre Ronco; Moin A. Saleem; Simon C. Satchell; Joshua M. Thurman

doi:10.1016/j.jtauto.2025.100342

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Autoantibodies reactive with glomerular endothelial cells and podocytes in patients with membranous nephropathy

Journal article

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Autoantibodies reactive with glomerular endothelial cells and podocytes in patients with membranous nephropathy

Vojtech Petr, Shrey Purohit, Felix Poppelaars, Brandon Renner, Jennifer Laskowski, Russell Whelan, Liudmila Kulik, Jessica Kendrick, Ashley Frazer-Abel, Diana Jalal, …

Journal of translational autoimmunity (Online), Vol.12, 100342

06/2026

DOI: 10.1016/j.jtauto.2025.100342

PMCID: PMC12767797

PMID: 41497346

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Abstract

Membranous nephropathy (MN) is a glomerular disease caused by autoantibodies reactive with podocyte antigens. The most common antigen is the M-type phospholipase A2 receptor (PLA2R), but autoantibodies to other podocyte antigens have also been identified. Investigators have reported elevated levels of complement fragments in plasma. However, most complement fragments generated on podocytes are likely to pass into the urine and not enter the bloodstream. Further, anti-PLA2R antibodies are usually IgG4 subclass and do not activate the classical pathway of complement. To look for additional autoantibodies capable of generating endovascular complement fragments, we examined whether MN patients have antibodies reactive with endothelial cell antigens. Retrospective cohort study. We analyzed plasma samples from 64 patients with MN, and results were compared to healthy controls and patients with chronic kidney disease. Plasma and urine complement activation fragments, glomerular endothelial cell and podocyte antibody binding assays, anti-cardiolipin antibody enzyme linked immunosorbent assay. Proteinuria, estimated glomerular filtration rate. Groups were compared with Wilcoxon, Kruskal-Wallis or chi-square tests. Correlations were performed using Pearson's correlation. Plasma C3a, C4a, C5a, and sC5b-9 levels were elevated in MN patients. Some patients had IgG reacted with glomerular endothelial cells or with podocytes. These antibodies were seen in distinct subsets of patients and did not correlate with the presence of anti-PLA2R antibodies. Higher titers of anti-glomerular endothelial cell antibodies correlated with systemic complement activation, seen by sC5b-9, and disease severity, determined by proteinuria. Anti-cardiolipin IgG levels associated with proteinuria. Assays used immortalized cell lines, and target antigens have not yet been identified. MN is a disease of autoimmunity directed against podocyte antigens, but some patients may also produce autoantibodies that target antigens on glomerular endothelial cells. The level of these antibodies correlates with adverse clinical findings.

Autoantibody

Complement

Glomerular endothelial cells

Membranous nephropathy

Details

Title: Subtitle: Autoantibodies reactive with glomerular endothelial cells and podocytes in patients with membranous nephropathy
Creators: Vojtech Petr - Institute of Clinical and Experimental Medicine
Shrey Purohit - University of Colorado Anschutz Medical Campus
Felix Poppelaars - University of Colorado Anschutz Medical Campus
Brandon Renner - University of Colorado Anschutz Medical Campus
Jennifer Laskowski - University of Colorado Anschutz Medical Campus
Russell Whelan - University of Colorado Anschutz Medical Campus
Liudmila Kulik - University of Colorado Anschutz Medical Campus
Jessica Kendrick - University of Colorado Anschutz Medical Campus
Ashley Frazer-Abel - University of Colorado Anschutz Medical Campus
Diana Jalal - University of Iowa
Barbara Marcolin - University of Colorado Anschutz Medical Campus
Isabelle Schmelzer - University of Colorado Anschutz Medical Campus
Hanna Debiec - Sorbonne Université
Pierre Ronco - Sorbonne Université
Moin A. Saleem - University of Bristol
Simon C. Satchell - University of Bristol
Joshua M. Thurman - University of Colorado Anschutz Medical Campus
Resource Type: Journal article
Publication Details: Journal of translational autoimmunity (Online), Vol.12, 100342
DOI: 10.1016/j.jtauto.2025.100342
PMID: 41497346
PMCID: PMC12767797
NLM abbreviation: J Transl Autoimmun
ISSN: 2589-9090
eISSN: 2589-9090
Publisher: Elsevier B.V
Grant note: National Institutes of Health: R01DK076690, DK133240, DK138960, DK130255
This work was supported by National Institutes of Health Grants R01DK076690 (JMT) , DK133240 (JMT and DJ) , DK138960 (JMT) , and DK130255 (JMT and JK) .
Language: English
Electronic publication date: 12/09/2025
Date published: 06/2026
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9985093889202771

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