PXD070406-1

PXD070406 is an original dataset announced via ProteomeXchange.

Title	IgM hyposialylation drives podocyte injury in pediatric and young adult patients with podocytopathies
Description	Altered immunoglobulin glycosylation has been implicated in antibody-mediated podocytopathies, yet the functional impact of IgM sialylation remains unclear. Previous evidence suggested that circulating cationic or hyposialylated IgM may contribute to podocyte injury in idiopathic nephrotic syndrome (iNS). Serum IgM from pediatric and young adult patients with podocytopathies, membranous nephropathy (MN), lupus nephritis (LN), and healthy controls were analyzed by lectin-based ELISA using a panel of six biotinylated lectins to detect terminal N-glycan residues. Among these, Sambucus nigra agglutinin (SNA) binds α2,6-linked sialic acid, and Ricinus communis agglutinin I (RCA-I) recognizes β1,4-linked galactose. Serum levels of the α2,6-sialyltransferase ST6GAL1 and the sialidases neuraminidase-1 (NEU1) and neuraminidase-3 (NEU3) were quantified. Cultured human podocytes were exposed to patient-derived, control, or enzymatically modified IgM (desialylated/resialylated) and analyzed by confocal microscopy, quantitative proteomics, phosphoproteomics, and metabolic assays. IgM from patients with podocytopathies showed reduced SNA binding, which inversely correlated with proteinuria (r = −0.69, P < 0.0001) and with serum sialidases NEU1/NEU3 (r = −0.67/−0.59, P < 0.0001). In paired samples, SNA reactivity decreased during relapse and normalized in remission, indicating dynamic modulation with disease activity. ST6GAL1 was undetectable in all groups. In contrast, PLA2R1-positive MN, in which pathogenic antibodies target podocyte PLA2R1, displayed reduced RCA-I binding. Podocytes exposed to hyposialylated or desialylated IgM exhibited actin disorganization, loss of nephrin signal, increased lipid peroxidation, and decreased ATP synthesis. In contrast, resialylated IgM preserved morphology and metabolism comparable to controls. Proteomic and phosphoproteomic profiling revealed enrichment of MAPK, mTOR, AMPK, and cytoskeletal remodeling pathways. IgM hyposialylation, driven by extracellular sialidases up-regulation, correlates with disease activity and promotes oxidative stress, mitochondrial dysfunction, and cytoskeletal remodeling in podocytes, identifying immune glycan remodeling as a modifiable determinant of podocyte injury and a potential biomarker of disease activity.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-28_16:39:15.377.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicole Grinovero
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-06 06:47:36	ID requested
⏵ 1	2026-06-28 16:39:16	announced

10.1016/j.ekir.2026.106598;

Spinelli S, Gaudiano S, Garbarino A, Lugani F, La Porta E, Petretto A, Bartolucci M, Lavarello C, Grinovero N, Musante I, Scudieri P, Trivelli A, Piaggio G, Magnasco A, Degl'Innocenti ML, Granata S, Zaza G, Verrina E, Candiano G, Bruschi M, IgM Hyposialylation Modulates Podocyte Vulnerability in Patients With Idiopathic Nephrotic Syndrome. Kidney Int Rep, 11(8):106598(2026) [pubmed]

submitter keyword: immunoglobulin M glycosylation, hyposialylation, sialidase, podocyte injury,podocytopathies

Andrea Petretto
contact affiliation	Core Facility for Omics Sciences, IRCCS Istituto Giannina Gaslini, Genoa, Italy
contact email	andreapetretto@gaslini.org
lab head
Nicole Grinovero
contact affiliation	IRCCS Istituto Giannina Gaslini
contact email	nicolegrinovero@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD070406

PRIDE project URI

• PRIDE
  1. PXD070406
     1. Label: PRIDE project
     2. Name: IgM hyposialylation drives podocyte injury in pediatric and young adult patients with podocytopathies