PXD074533-1

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

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PRIDE project URI

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