PXD069403

PXD069403 is an original dataset announced via ProteomeXchange.

Title	Exosome-Based Proteomic Profiling for Biomarker Discovery in Pediatric Fabry Disease: Insights into Early Diagnosis Monitoring
Description	Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by GLA mutations, leading to deficient α-galactosidase A (α-Gal A) activity and progressive glycosphingolipid accumulation. While α-Gal A activity is the diagnostic gold standard, its sensitivity is reduced in late-onset or heterozygous patients. Conventional biomarkers such as lyso-Gb3 provide only limited insight into disease progression and therapeutic response. Exosomes, as stable carriers of disease-specific proteins, may offer complementary biomarkers for early detection and longitudinal monitoring. Methods: 21 pediatric FD patients with confirmed GLA mutations were enrolled. Clinical, enzymatic, renal, and cardiac parameters were assessed. Plasma-derived exosomes were characterized by transmission electron microscopy and proteomic profiling. Differentially expressed proteins were identified by mass spectrometry, analyzed by GO/KEGG enrichment, and validated using RT-PCR, ELISA, and immunofluorescence in patient samples and Gla-/- mice. Results: Male patients showed markedly reduced α-Gal A activity and elevated lyso-Gb3 compared to females. Although overt renal and cardiac dysfunction was uncommon, several patients exhibited early abnormalities such as proteinuria, elevated LVMI, or increased cTnI. Proteomic analysis identified 2,553 proteins, of which 188 were differentially expressed. Fibrosis- and inflammation-related proteins including THBS1 and CFHR5 were upregulated, while protective factors such as APM1, SERPINA10, and CAB39 were downregulated. IGFBP3 was also elevated and closely linked to tissue remodeling. Enriched pathways involved PPAR/AMPK signaling, lipid metabolism, and complement activation. Conclusions: Exosomal proteomic profiling reveals early molecular signatures of cardiorenal involvement in pediatric FD. Key proteins such as THBS1, CFHR5, IGFBP3, APM1, and CAB39 show strong potential as biomarkers for risk stratification, disease monitoring, and therapeutic evaluation.
HostingRepository	PRIDE
AnnounceDate	2025-12-08
AnnouncementXML	Submission_2025-12-07_16:22:41.410.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yu Xia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	6220 Time-of-Flight LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-13 09:22:33	ID requested
⏵ 1	2025-12-07 16:22:42	announced

10.3390/biomedicines13112598;

Lu Z, Xia Y, Wang B, Jiang P, Mao J, Exosome-Based Proteomic Profiling for Biomarker Discovery in Pediatric Fabry Disease: Insights into Early Diagnosis Monitoring. Biomedicines, 13(11):(2025) [pubmed]

submitter keyword: Child,Fabry disease, Exosome, Biomarkers

Yu Xia
contact affiliation	Jiang Pingping Laboratory, School of Basic Medical Sciences, Zhejiang University School of Medicine
contact email	12218528@zju.edu.cn
lab head
Yu Xia
contact affiliation	Zhejiang university
contact email	12218528@zju.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069403
     1. Label: PRIDE project
     2. Name: Exosome-Based Proteomic Profiling for Biomarker Discovery in Pediatric Fabry Disease: Insights into Early Diagnosis Monitoring