PXD047421

PXD047421 is an original dataset announced via ProteomeXchange.

Title	Anti-nephrin autoantibodies in minimal change disease and focal segmental glomerulosclerosis (phospho-proteomics)
Description	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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:42:55.855.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Moritz Lassé
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-30 14:32:14	ID requested
1	2024-05-27 01:12:02	announced
⏵ 2	2024-10-22 06:42:56	announced	2024-10-22: Updated project metadata.

10.1056/NEJMOA2314471;

submitter keyword: focal segmental glomerulosclerosis (FSGS), proteomics, minimal change disease (MCD), autoantibodies, phospho-proteomics,kidney disease, nephrin

Prof. Dr. Markus M. Rinschen
contact affiliation	III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
contact email	m.rinschen@uke.de
lab head
Moritz Lassé
contact affiliation	Zentrum für Innere Medizin, III. Medizinische Klinik und Poliklinik (Nephrologie/Rheumatologie/Endokrinologie), Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany
contact email	moritz.lasse@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047421
     1. Label: PRIDE project
     2. Name: Anti-nephrin autoantibodies in minimal change disease and focal segmental glomerulosclerosis (phospho-proteomics)