PXD062941

PXD062941 is an original dataset announced via ProteomeXchange.

Title	Proteomic Discoveries in hypermobile Ehlers Danlos Syndrome (hEDS) Reveals Insights into Disease Pathophysiology
Description	Objectives: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a prevalent but poorly understood connective tissue disorder lacking molecular diagnostic markers. This study aimed to identify proteomic biomarkers in hEDS to elucidate underlying pathophysiology and support objective diagnostic and therapeutic strategies. Methods: We conducted an unbiased serum proteomic analysis using mass spectrometry on female hEDS patients (n=29) and matched controls (n=29), followed by pathway enrichment and gene ontology analysis. Key findings were validated in an expanded cohort (n=41 hEDS, n=38 controls) via ELISA for complement proteins (C1QA, C3, C8A, C8B, C9) and cytokine array profiling of 105 immune mediators (n=13 per group). Results: Proteomic analysis revealed 35 differentially expressed proteins in hEDS, with 43% involved in the complement cascade and 80% linked to immune, coagulation, or inflammatory pathways. Pathway analyses confirmed enrichment in complement activation, coagulation, and stress responses. ELISA validation showed significant reductions in C1QA, C3, C8A, C8B, and C9 in hEDS patients, consistent across age and sex. Cytokine profiling identified elevated IGFBP-2, SERPINE1, and IL-11, and decreased IL-8, supporting a model of dysregulated immune activation and poor inflammation resolution. Conclusions: Our findings implicate systemic immune dysregulation, particularly involving the complement system and pro-fibrotic cytokines, as a central feature of hEDS pathophysiology. These results challenge the view of hEDS as solely a connective tissue disorder and support a revised paradigm that includes innate immune dysfunction. Objective biomarkers identified here may improve diagnostic accuracy and highlight novel therapeutic targets for this underdiagnosed condition.
HostingRepository	PRIDE
AnnounceDate	2025-09-29
AnnouncementXML	Submission_2025-09-28_18:07:03.790.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Bethard
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-14 10:37:53	ID requested
⏵ 1	2025-09-28 18:07:04	announced

10.1093/immhor/vlaf044;

Griggs M, Daylor V, Petrucci T, Weintraub A, Huff M, Willey S, Byerly K, Loizzi B, Morningstar J, Ball LE, Bethard JR, Drake R, Sharma A, Eichinger JK, Nichols M, Kautz S, Shapiro S, Maitland A, Patel S, Norris RA, Gensemer C, Proteomic discoveries in hypermobile Ehlers-Danlos syndrome reveal insights into disease pathophysiology. Immunohorizons, 9(10):(2025) [pubmed]

submitter keyword: Ehlers Danlos Syndrome (hEDS) , DIA,Serum, ELISA

Cortney Gensemer
contact affiliation	Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, 29407 Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, 29407
contact email	gensemer@musc.edu
lab head
Jennifer Bethard
contact affiliation	Medical University of SC
contact email	bethard@musc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062941
     1. Label: PRIDE project
     2. Name: Proteomic Discoveries in hypermobile Ehlers Danlos Syndrome (hEDS) Reveals Insights into Disease Pathophysiology