Proteomic discoveries in hypermobile Ehlers–Danlos syndrome reveal insights into disease pathophysiology, 2025, Griggs et al.

C

Chandelier

Senior Member (Voting Rights)

Molly Griggs, Victoria Daylor, Taylor Petrucci, Amy Weintraub, Matthew Huff, Sofia Willey, Kathryn Byerly, Brian Loizzi, Jordan Morningstar, Lauren Elizabeth Ball,
Jennifer R Bethard, Richard Drake, Amol Sharma, Josef K Eichinger, Michelle Nichols, Steven Kautz, Steven Shapiro, Anne Maitland, Sunil Patel, Russell A Norris, Cortney Gensemer


Abstract​

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 analyzed through pathway enrichment and gene ontology pipelines. Prioritized candidate biomarker proteins were verified in expanded patient and control cohorts via ELISA.
Cytokine array profiling was conducted to assess immune signaling patterns. 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 revealed alterations in nodal immune cell mediators in hEDS patients, supporting a model of dysregulated inflammatory response.
Our findings indicate a systemic immune dysregulation, particularly involving the complement system and profibrotic cytokines, as a common feature in hEDS pathophysiology.
These findings challenge the traditional view of hEDS as solely a connective tissue disorder and support a revised paradigm that includes innate immune dysfunction.
This immune involvement may contribute to disease pathophysiology and inform the development of biologically based diagnostic tools, enabling earlier diagnosis and guiding future therapeutic strategies.
 
This is not EDS. They had 90% of patients female and EDS, being monogenic, is either with equal sex ratio (dominant on an ordinary chromosome) or x-linked recessive with a large male predominance.

Anything that is not monogenic is a rag bag of polygenic states, which needs to be called something else.

This reminds me of the 'research' i was introduced to in the context of hypermobility in 1979. The study ended up proving a contradiction because the investigator didn't understand what diagnosis entailed.

Similarly this study simply shows that hEDS isn't hEDS, which we knew anyway. So the result is a lemon.
 
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