PXD074533

PXD074533 is an original dataset announced via ProteomeXchange.

Title	STEROID-RESISTANT IDIOPATHIC NEPHROTIC SYNDROME DEFINES A DISTINCT MALADAPTIVE MOLECULAR STATE.
Description	INTRODUCTION: Idiopathic nephrotic syndrome (iNS) shows marked variability in treatment response, yet the molecular basis of multidrug resistance remains unclear. We hypothesized that multidrug-resistant nephrotic syndrome (MRNS) represents a distinct biological state rather than simply severe disease activity. METHODS: Serum proteomic profiling (LC–MS/MS) was performed in 165 pediatric and young adult patients with iNS, stratified by therapeutic phenotype (MRNS, steroid-dependent [SDNS], and multidrug-dependent [MDNS]). Differential protein expression was analyzed using pathway enrichment and machine learning–based approaches. Key biomarkers were validated by ELISA. Functional effects were evaluated in human podocytes exposed to patient-derived sera and in their peripheral blood mononuclear cells (PBMCs). RESULTS: Of 810 identified proteins, 322 differed significantly among groups. A 35-protein Random Forest signature discriminated MRNS from SDNS and MDNS. Integration of machine learning approaches identified dystroglycan 1 (DAG1), CD44 antigen (CD44), and RISC-loading complex subunit (TARBP2) as major contributors to group separation. Functional analyses revealed cytoskeletal disorganization, altered autophagy, inflammasome dysregulation, and increased endoplasmic reticulum stress in podocytes exposed to MRNS sera. A central mechanistic axis was the stress–survival imbalance with inverse regulation of the endoplasmic reticulum chaperon BIP (GRP78) and phosphorylated AKT (Ser473), a pattern also observed in peripheral blood mononuclear cells from MRNS patients. In contrast, sera from patients in remission showed phenotypes similar to those of healthy donors. CONCLUSIONS: MRNS represents a distinct molecular state characterized by systemic and organ-persistent stress activation and disrupted cellular homeostasis, whereas remission is characterized by a near-healthy profile. These findings support biomarker-guided stratification and therapeutic strategies aimed at restoring cellular balance rather than broadly suppressing immunity.
HostingRepository	PRIDE
AnnounceDate	2026-07-16
AnnouncementXML	Submission_2026-07-16_00:56:11.764.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Bartolucci
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-16 15:52:24	ID requested
⏵ 1	2026-07-16 00:56:12	announced

10.1016/J.EKIR.2026.106617;

submitter keyword: idiopathic nephrotic syndrome, Multidrug resistance, Podocyte injury, Proteome, Mass spectrometry

Andrea Petretto
contact affiliation	IRCCS Istituto G Gaslini
contact email	a.petretto@gmail.com
lab head
Martina Bartolucci
contact affiliation	IRCCS Gaslini
contact email	smartibartolucci@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/2026/07/PXD074533

PRIDE project URI

• PRIDE
  1. PXD074533
     1. Label: PRIDE project
     2. Name: STEROID-RESISTANT IDIOPATHIC NEPHROTIC SYNDROME DEFINES A DISTINCT MALADAPTIVE MOLECULAR STATE.