Proteomics

Dataset Information

0

Anti-nephrin autoantibodies in minimal change disease and focal segmental glomerulosclerosis (phospho-proteomics)


ABSTRACT: Background: Minimal change disease (MCD) and focal-segmental glomerulosclerosis (FSGS) are immune-mediated glomerular diseases manifesting as nephrotic syndrome. Autoantibodies against the podocyte slit diaphragm protein nephrin were recently identified in a subset of patients with minimal change disease, but their clinical and pathophysiological significance is largely unknown. Methods: Using immunoprecipitation assays, we performed a blinded screening for anti-nephrin antibodies in diagnostic and follow-up serum samples from adult patients with biopsy-proven MCD, FSGS, IgA nephropathy, and membranous nephropathy in comparison to healthy controls in two independent patient cohorts from Hamburg, Germany, and Bari, Italy. We further established a mouse model of anti-nephrin antibody-induced disease by active immunization using the recombinant murine nephrin ectodomain. Results: Anti-nephrin autoantibodies were detected in 50 of 110 (45%) patients with MCD, 8 of 107 (7%) patients with FSGS, 1 of 50 (2%) patients with membranous nephropathy, 0 of 48 (0%) patients with IgA nephropathy, and 0 of 67 (0%) healthy individuals. During follow-up, presence, and absence of anti-nephrin autoantibodies in patients with MCD and FSGS strongly correlated with active disease and remission, respectively. Immunization of mice induced anti-nephrin autoantibody formation and a highly dynamic phenotype with severe nephrotic syndrome and the histological features of MCD. Mechanistically, anti-nephrin autoantibodies induced nephrin phosphorylation at Tyr1191, cytoskeletal rearrangement, and downregulation of key podocyte proteins. Conclusion: Anti-nephrin antibodies are a valuable biomarker of disease activity in patients with MCD and FSGS, and binding of anti-nephrin antibodies at the podocyte slit diaphragm induces MCD with nephrotic syndrome.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Glomerular Cell, Kidney, Renal Glomerulus

DISEASE(S): Focal Segmental Glomerulosclerosis

SUBMITTER: Moritz Lassé  

LAB HEAD: Prof. Dr. Markus M. Rinschen

PROVIDER: PXD047421 | Pride | 2024-05-27

REPOSITORIES: Pride

Similar Datasets

2024-05-27 | PXD047417 | Pride
2024-07-15 | PXD053362 | Pride
2017-01-04 | E-GEOD-69814 | biostudies-arrayexpress
2023-01-25 | GSE216841 | GEO
2014-11-04 | E-GEOD-57099 | biostudies-arrayexpress
2017-06-20 | GSE100185 | GEO
2022-06-22 | GSE206525 | GEO
2017-01-04 | GSE69814 | GEO
2021-02-16 | GSE145969 | GEO
2022-12-22 | PXD028536 | Pride