The EDS Society announced a promising breakthrough in research they funded published September 3, 2024 by a group of Italian scientists in the American Journal of Genetics using their HEDGE registry for the US cohort. Scientists have identified a specific protein in the blood that appears to be present at higher levels in individuals with the most common type of EDS: specifically hypermobile Ehlers-Danlos Syndrome (hEDS) and as well as Hypermobility Spectrum Disorders (HSD). This protein is linked to the body’s process of collagen synthesis and repair, which is believed to be the faulty in hypermobile patients. The overall findings mark the identification of potential biomarkers in the blood that could help in diagnosing these conditions in the future. The EDS Society says, “This discovery is significant because diagnosing hEDS and HSD has been challenging due to the lack of established laboratory tests and molecular markers.”

Research Methodology:

• Sample Group: The research team, led by scientists at the University of Brescia in Italy, looked at these protein fragments in the blood of 174 patients from Italy and the U.S. A total of 94 — 86 women and eight men — met the full criteria for a hEDS diagnosis, according to a 2017 classification of EDS. The other 80 patients, comprising 68 women and 12 men, did not meet those criteria and were diagnosed with HSD. The study also included blood samples from patients with either of two other types of EDS or with joint diseases, such as rheumatoid arthritis, psoriatic arthritis, and osteoarthritis, as well as healthy people who were unrelated to anyone with hEDS or HSD.
• Procedure: Researchers measured the levels of the newly identified protein in the blood samples from all participants.
• Findings: The protein levels were significantly higher in those with hEDS and HSD, correlating with the severity of their symptoms (not observed in the control group). The unique pattern of protein fragments of fibronectin and collagen found in blood suggest that hEDS or HSD may share molecular mechanisms and be in fact the same disease. This challenges the current thinking about how hEDS and HSD are classified.

Though it’s a small cohort, this discovery could lead to more research and potentially the development of a blood test for hypermobile EDS (and HSD), making it easier to diagnose the syndrome, especially in cases where symptoms are ambiguous or overlap with other conditions. Early and accurate diagnosis could significantly improve management strategies and outcomes for these conditions.

Authors outline the significance of their findings in the below excerpt from the study…

“Our study builds upon a growing body of evidence suggesting that hEDS and HSD are not distinct disorders but rather represent variants of the same entity (Chiarelli et al. 2019; Chiarelli, Zoppi, Ritelli, et al. 2021; Chiarelli, Zoppi, Venturini, et al. 2021; Ritelli et al. 2022, 2024; Zoppi et al. 2018). This perspective is reinforced by our current findings, which revealed a shared pathophysiological mechanism characterized by excessive ECM breakdown, observed through the identification of FN and COLLI degradation fragments in plasma. While we recognize the need for validation studies, our findings represent a significant milestone in the field of hypermobility syndromes…Our discovery holds the promise for introducing the first and only blood test to definitively diagnose hEDS/HSD, the potential clinical implications of this breakthrough are extensive. Indeed, it could significantly improve diagnostic pathways, leading to the inclusion of more individuals in appropriate medical care, reduce diagnostic delays by increasing healthcare professionals’ confidence in identifying the condition, and have substantial impacts on legal settings, insurance payment policies, and various other healthcare areas… We are confident that our recently published proposals to improve the diagnostic criteria for hEDS (Ritelli et al. 2024) will be considered by this committee, especially now that we have potentially identified a common biomarker for hEDS and HSD.”

Further Research Needed: More extensive studies are needed to validate these findings across a broader demographic and a larger cohort and to test across all subtypes of EDS. The Ehlers-Danlos Society is now supporting confirmatory studies.

Validity and Reliability: While the initial results are promising, this is still in the early stages of research. The validity and reliability of this potential test will depend on subsequent studies and trials, which will need to replicate these findings under diverse conditions and in larger populations.

Learn More
For more, read the news from the EDS Society or read the research paper:
“Bridging the Diagnostic Gap for Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders: Evidence of a Common Extracellular Matrix Fragmentation Pattern in Patient Plasma as a Potential Biomarker.”  Authors: Marco Ritelli, Nicola Chiarelli, Valeria Cinquina, Valeria Bertini, Silvia Piantoni, Alessia Caproli, Silvia Ebe Lucia Della Pina, Franco Franceschini, Guido Zarattini, Woodrow Gandy, Marina Venturini, Nicoletta Zoppi,  Marina Colombi.  https://doi.org/10.1002/ajmg.a.63857