PXD053837

PXD053837 is an original dataset announced via ProteomeXchange.

Title	Unbiased Proteomic Analysis for Real-Life Identification of Podocyte Antigens and Disease Mechanisms in Membranous NephropathyUnbiased Proteomic Analysis for Real-Life Identification of Podocyte Antigens and Disease Mechanisms in Membranous Nephropathy
Description	Background: In recent years, an innovative strategy using laser microdissection and mass spectrometry markedly expanded the landscape of antigens associated with membranous nephropathy (MN). Specific associations with phenotypes, diseases and sometimes reversible triggers led to a novel antigen-based classification of MN, paving the way for precision medicine and stressing the need for more routine use of proteomics in MN. Methods: To explore the proteomic landscape of human glomeruli and identify podocyte antigens and disease mechanisms in MN, we expanded the original technique to an integrative approach combining laser capture microdissection, next-generation mass spectrometry and computational analysis. Next to conventional data-dependent acquisition (DDA), we used and assessed the diagnostic yield of the more comprehensive data-independent acquisition (DIA) mass spectrometry, which enables the detection and quantification of every peptide in a sample irrespective of its level of abundance or m/z value. Our proteomic pipeline was applied to residual material from kidney biopsies in 64 individuals, including 31 healthy controls; 5 disease controls; 5 PLA2R-associated MN; and 23 PLA2R-negative MN. Results: Unbiased analyses confirmed the significant enrichment in PLA2R, IgG4 and complement proteins in glomeruli from patients with PLA2R-MN compared with healthy and disease controls, while molecular characterization of complement fragments provided evidence for complement activation in PLA2R-MN. Compared to DDA, DIA mass spectrometry increased the number of glomerular proteins (~3800 vs. ~1200) identified in healthy glomeruli; allowed the detection all known antigens except NELL1 in normal glomeruli; and increased the detection rate of podocyte antigens from 50% to >80% in PLA2R-negative MN. Conclusions: This proof-of-concept study suggests that an integrative approach combining laser microdissection, DIA mass spectrometry and computational biology is a powerful tool, with translational potential, to identify podocyte antigens and unravel disease mechanisms in MN.
HostingRepository	PRIDE
AnnounceDate	2025-03-07
AnnouncementXML	Submission_2025-03-07_03:56:35.357.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD053837
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Didier Vertommen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-10 01:40:13	ID requested
⏵ 1	2025-03-07 03:56:35	announced

10.6019/PXD053837;

10.1053/J.AJKD.2025.01.014;

submitter keyword: : kidney disease

membranous nephropathy

autoimmunity

proteomics

computational analysis.

Prof Johann Morelle
contact affiliation	Division of Nephrology, University Hospitals Namur | Place Louise Godin 15, B-5000 Namur, Belgium
contact email	johann.morelle@chuuclnamur.uclouvain.be
lab head
Didier Vertommen
contact affiliation	UCL - de Duve Institute, Brussels Belgium
contact email	didier.vertommen@uclouvain.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053837
     1. Label: PRIDE project
     2. Name: Unbiased Proteomic Analysis for Real-Life Identification of Podocyte Antigens and Disease Mechanisms in Membranous NephropathyUnbiased Proteomic Analysis for Real-Life Identification of Podocyte Antigens and Disease Mechanisms in Membranous Nephropathy