A recent 2026 study is providing additional clues about the biology of hypermobility spectrum disorder (HSD) and hypermobile Ehlers Danlos Syndrome (hEDS). In this article, we’ll explore what the researchers discovered, why they believe the two conditions may share common biological mechanisms, and what these findings could mean for future research.
How the Study Was Done
The authors took blood from the 352 participants and compared the expression of 458 circulating proteins between those with HSD and hEDS; between those with hEDS and healthy controls; and between those with HSD and healthy controls.
First, Let’s Define “Differentially Expressed”
Before diving into the results, it’s helpful to understand what the researchers mean by “differentially expressed proteins” (DEPs). They weren’t looking for proteins that existed only in people with hEDS or HSD. Rather, they compared the levels of the same proteins in both patients and healthy controls. If a protein was found at significantly higher or lower levels in one group than the other, it was considered “differentially expressed.” Proteins found at higher levels are described as upregulated, while those found at lower levels are described as downregulated. This doesn’t mean these proteins are necessarily “good” or “bad”. It simply means the body is producing more or less of it than healthy controls, which may provide important clues about how the disease works.
What They Found
The authors found 54 DEPs in hEDS compared to controls. 19 of those proteins were downregulated, and 35 were upregulated.
As for HSD, the authors found 49 DEPs between patients and controls. HSD patients showed 3 downregulated proteins and 46 upregulated proteins when compared to controls.
Importantly, the authors found no significant difference in proteins between HSD patients and hEDS patients. The authors stated that this “reinforc[es] the idea that hEDS and HSD share common protein signatures and a disease-associated profile that extends beyond variations in gene expression.” In other words, these diseases may have a similar mechanism and could potentially represent two points along the spectrum of the same disease.
Because there were no DEPs between HSD and hEDS patients, the authors combined these groups for further analysis to compare these patients against healthy controls. That comparison revealed 69 total DEPs, with 19 downregulated proteins and 50 upregulated proteins in the patients. Some of the proteins were involved in inflammation, the nervous system, cardiometabolic processes, tissue development and maintenance, and organ damage, suggesting that the changes seen in hEDS/HSD affect multiple body systems rather than just connective tissue. More specifically, they were linked to peripheral nervous system myelination, oxidative stress, regulation of certain immune cells, and inflammatory responses to antigens.
What Does This All Mean?
This study found that people with hEDS and HSD shared many of the same changes in blood protein levels compared with healthy people, while showing no detectable differences between the two conditions. While this study can’t tell us exactly why these proteins are altered, it does highlight several biological processes that may be involved in both conditions.
Key Takeaways
- People with hEDS and HSD showed no significant differences in their blood protein patterns.
- The results support the idea that hEDS and HSD may share common biological mechanisms and could represent different points along the same disease spectrum.
- The protein patterns suggest that chronic inflammation, changes in the environment surrounding nerves, and abnormalities in connective tissue may all play a role in hEDS/HSD.
- The study adds to growing evidence that hEDS and HSD are systemic conditions, affecting more than just connective tissue.
Final Thoughts
While this is only one study and its findings will need to be confirmed by larger studies, it represents an important step toward better understanding the biology of hEDS and HSD. Rather than relying only on clinical observations, researchers are beginning to identify measurable biological changes that may help explain how these conditions develop and affect multiple body systems.
Although these findings are not yet ready to change clinical practice, they provide an important foundation for future research. As scientists continue to study these protein patterns, they may help refine diagnostic criteria, support the development of laboratory-based tests, and guide more targeted treatments for people living with hEDS and HSD.
Clare Tyler, Author
Law Student, POTSise
& Rare Disease Patient
Edited by Jacqueline Teti, Editor-in-Chief
