Dataset Information

Proteomic Discoveries in hypermobile Ehlers Danlos Syndrome (hEDS) Reveals Insights into Disease Pathophysiology

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

DISEASE(S): Ehlers-danlos Syndrome

SUBMITTER: Jennifer Bethard

LAB HEAD: Cortney Gensemer

PROVIDER: PXD062941 | Pride | 2025-09-29

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	12282023_Norris_GR088816_Serum_QC_C3_P2.raw	Raw
	12282023_Norris_GR088816_Serum_QC_C4_P2.raw	Raw
	12282023_Norris_GR088816_Serum_QC_C5_P2.raw	Raw
	12282023_Norris_GR088816_Serum__10C_90.raw	Raw
	12282023_Norris_GR088816_Serum__11C_23.raw	Raw

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Proteomic discoveries in hypermobile Ehlers-Danlos syndrome reveal insights into disease pathophysiology.

Griggs Molly M Daylor Victoria V Petrucci Taylor T Weintraub Amy A Huff Matthew M Willey Sofia S Byerly Kathryn K Loizzi Brian B Morningstar Jordan J Ball Lauren Elizabeth LE Bethard Jennifer R JR Drake Richard R Sharma Amol A Eichinger Josef K JK Nichols Michelle M Kautz Steven S Shapiro Steven S Maitland Anne A Patel Sunil S Norris Russell A RA Gensemer Cortney C

ImmunoHorizons 20250901 10

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a poorly understood connective tissue disorder that lacks molecular diagnostic markers. This study aimed to identify proteomic signatures associated with hEDS to define underlying pathophysiology and to inform objective diagnostic strategies with therapeutic potential. An unbiased mass spectrometry-based proteomic analysis of serum from female hEDS patients (n = 29) and matched controls (n = 29) was conducted. Differentially abundant proteins were ana ...[more]

PMID: 40972649

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