Proximity extension assay-based serum proteomic profiling identifies shared protein signatures in hypermobile Ehlers–..., 2026, Cinquina et al.

[ME/CFS Science Blog]

Abstract​

Background​

Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are prevalent conditions characterized by symptomatic joint hypermobility and a substantial public health burden, for which no causal treatment is currently available. In the absence of a defined molecular basis or validated diagnostic biomarkers, diagnosis of hEDS relies solely on the 2017 clinical criteria, with individuals who do not meet these criteria classified as HSD. Although currently categorized as distinct entities, the biological relationship between hEDS and HSD remains a subject of active debate within the scientific community.

Methods​

We performed targeted serum proteomic profiling using the proximity extension assay technology, quantifying 458 proteins in large cohorts of hEDS (n = 88) and HSD (n = 88) patients, alongside healthy controls (n = 176).

Results​

Compared to controls, 54 proteins were differentially expressed in hEDS patients and 49 in HSD patients. No statistically significant differences were observed between hEDS and HSD groups. When the combined patient cohort was analyzed, 69 proteins showed differential expression relative to controls. The proteins were distributed across the predefined PEA panels, which include proteins involved in inflammatory, cardiometabolic, neurological, organ damage, and developmental processes.

Conclusions​

This targeted serum proteomic analysis identified overlapping protein expression changes in hEDS and HSD relative to controls, while revealing no detectable differences between the two conditions. These findings suggest the presence of shared molecular features across the hEDS/HSD spectrum and identify a set of candidate circulating proteins that warrant further investigation and independent validation in larger, well-characterized cohorts.

Link:

Proximity extension assay-based serum proteomic profiling identifies shared protein signatures in hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders - Clinical Proteomics

Background Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are prevalent conditions characterized by symptomatic joint hypermobility and a substantial public health burden, for which no causal treatment is currently available. In the absence of a defined...

link.springer.com

 

[Jonathan Edwards]

These findings suggest the presence of shared molecular features across the hEDS/HSD spectrum and identify a set of candidate circulating proteins that warrant further investigation and independent validation in larger, well-characterized cohorts.

Maybe, or maybe they just illustrate that using statistics you can always find a difference between a chosen group and 'controls'. Maybe they should have used a control group with an equivalent level of symptoms but no hypermobility. This may be a group of not so healthy people who by chance happen to have loose joints.

 

[ME/CFS Science Blog]

Main results in Figure 2:

 

[ME/CFS Science Blog]

To explore the biological consequences of these protein changes, the 69 DEPs were subject to GO functional enrichment analyses (Fig. 2D). The most representative KEGG biological processes including positive regulation of MAPK cascade, response to oxidative stress, Schwann cell development, regulation of T cell activation, and inflammatory response to antigenic stimulus, emerged as the most significantly affected biological functions.

A previous proteomics study mostly pointed to the complement system, so while this is potentially related it's not exactly a replication:
Proteomic discoveries in hypermobile Ehlers-Danlos syndrome reveal insights into disease pathophysiology - PubMed

 

[SNT Gatchaman]

Some of the isoforms of carbonic anhydrase making an appearance in that volcano plot.

 

[Jonathan Edwards]

Some of the isoforms of carbonic anhydrase making an appearance in that volcano plot.

Yes. But I guess those are real anhydrases and functionally unrelated to CA10?
It might be a sign that that set of genes is biased to show up on GWAS for some spurious reason, I guess, maybe because of a lot of polymorphism or something.

 

[forestglip]

Yes. But I guess those are real anhydrases and functionally unrelated to CA10?

Yes, from my reading about CA10, as far as I know there are no known overlapping functions between the catalytic isoforms and the acatalytic CA8, CA10, and CA11, which don't appear to be in that chart.