New study suggests hypermobile EDS and HSD may share a disease spectrum
Serum analysis shows overlapping protein changes in both conditions
Written by |
Proteins in the serum of adults with hypermobile Ehlers–Danlos syndrome (EDS) show patterns similar to those in adults with hypermobility spectrum disorder (HSD), with dozens differing from healthy individuals, supporting the idea that they may be part of a shared disease spectrum in a study with patients from the U.S. and Italy.
These findings provide “a novel molecular perspective” on these two diseases, which have overlapping symptoms, researchers wrote in “Proximity extension assay-based serum proteomic profiling identifies shared protein signatures in hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders,” published in Clinical Proteomics.
Hypermobile EDS and HSD share symptoms, lack clear biomarkers
Like other types of EDS, hypermobile EDS affects the body’s connective tissues, which help support joints and other structures. It is mainly characterized by joint hypermobility, musculoskeletal symptoms, and a range of other health issues. These symptoms can overlap with those of other conditions, often delaying diagnosis. People with symptomatic hypermobile joints who do not fully meet the criteria for EDS are classified as having HSD.
Although hypermobile EDS and HSD are classified separately, some researchers believe they may represent different points along the same disease spectrum. However, their biology remains incompletely understood, and neither condition has validated diagnostic biomarkers, such as specific proteins in serum, that can confirm the diagnosis.
“In clinical practice, diagnosing, classifying, and managing hEDS and HSD patients remains extremely challenging,” the scientists wrote. “Patients frequently face prolonged diagnostic pathways characterized by uncertainty and vulnerability, particularly individuals with HSD in countries where this condition is not formally recognized within public healthcare systems.”
To explore this question, the researchers analyzed serum samples from adults with hypermobile EDS or HSD. They used a technique called targeted proteomic profiling, which measures specific proteins, using the proximity extension assay — a method that can detect them in a small sample with high sensitivity. In total, the researchers measured 458 different proteins.
In the study, the researchers compared these proteins in 88 adults with hypermobile EDS and 88 adults with HSD. In both groups, half of patients were from the U.S. and half from Italy. Most were women, and the mean ages were similar in the two groups (36 vs. 38 years). Proteins also showed similar patterns, “reinforcing the idea that [hypermobile EDS] and HSD share common protein signatures,” the researchers wrote.
Researchers compare patients with healthy individuals
The study also included 176 healthy individuals from Italy, with a mean age of 42, as controls. Compared with these controls, 54 proteins were differentially expressed in hypermobile EDS and 49 in HSD. A differentially expressed protein means its level in the serum is higher or lower than normal. Most of these proteins were increased — 35 in hypermobile EDS and 46 in HSD.
When patients from both groups were analyzed together, 69 proteins were differentially expressed compared with the controls. These proteins were spread across assay panels related to inflammation, cardiometabolic function (how the heart and blood vessels use energy), neurological processes, organ damage, and development.
“This targeted serum proteomic analysis identified overlapping protein expression changes in [hypermobile EDS] and HSD relative to controls, while revealing no detectable differences between the two,” the researchers wrote, supporting the idea that they may belong to the same disease spectrum.
The findings also “identify a set of candidate circulating proteins that warrant further investigation and independent validation in larger, well-characterized cohorts,” they added.
