PXD071992-1

PXD071992 is an original dataset announced via ProteomeXchange.

Title	Mapping the IgG Interactome in Circulating Immune Complexes Identifies Serum Diagnostic Biomarkers for Narcolepsy and Idiopathic Hypersomnia
Description	Immunoglobulin G-containing circulating immune complexes (IgG-CICs) play pivotal roles in immune-related diseases; however, their interaction networks and diagnostic potential in central disorders of hypersomnolence (CDH), including narcolepsy type 1 and type 2 (NT1/NT2) and idiopathic hypersomnia (IH), remain inadequately understood. This study aimed to systematically profile the IgG interactome within serum CICs and to evaluate its utility as a source of diagnostic biomarkers for CDH. To this end, we first employed crosslinking mass spectrometry to map the direct IgG interaction network, identifying 26 high-confidence direct interactors and establishing the impact of pre-analytical conditions (temperature and time) on interaction stability. Comparative proteomic analysis of IgG-CICs from CDH patients and normal controls (NC) using four-dimensional data-independent acquisition mass spectrometry uncovered numerous disease-specific differentially expressed proteins and dysregulated pathways, including the complement system, cholesterol metabolism, and neutrophil extracellular trap formation. Candidate biomarkers were validated through parallel reaction monitoring. Leveraging these validated markers, multivariable and LASSO regression-based diagnostic models demonstrated robust discriminative performance, achieving high area under the curve (AUC) values, particularly in distinguishing NT2 and IH from NC. These models also effectively differentiated disease subtypes, such as NT1 from the combined NT2 and IH group. Overall, this study provides the first comprehensive map of the direct IgG-CIC interactome in CDH, identifies distinct subtype-specific molecular signatures, implicates complement dysregulation and metabolic alterations as key pathological mechanisms, and establishes robust serum biomarker panels for differential diagnosis, thereby positioning IgG-CICs as a promising source for noninvasive diagnostic tools in sleep disorders.
HostingRepository	iProX
AnnounceDate	2025-12-13
AnnouncementXML	Submission_2025-12-14_22:36:43.096.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jian Zhou
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X; Q Exactive Plus; TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-14 22:35:26	ID requested
⏵ 1	2025-12-14 22:36:43	announced

Dataset with its publication pending

submitter keyword: Circulating immune complexes, Proteomics, Narcolepsy, Idiopathic hypersomnia, Biomarkers, Diagnostic model

Jian Zhou
contact affiliation	Chongqing Medical University
contact email	zhoujian@cqmu.edu.cn
lab head
Jian Zhou
contact affiliation	Chongqing Medical University
contact email	zhoujian@cqmu.edu.cn
dataset submitter

iProX dataset URI