New Research Identifies Potential Biomarkers for Diagnosing Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders

A recent study funded by The Ehlers-Danlos Society, and published in the American Journal of Medical Genetics, has identified potential blood-based biomarkers that could help diagnose hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). This discovery is significant because diagnosing hEDS and HSD has been challenging due to the lack of established laboratory tests and molecular markers.

Study Overview

In this study, researchers examined blood samples from 466 adults, including 94 diagnosed with hEDS and 80 with HSD. The study revealed the presence of a specific 52 kDa fragment of fibronectin in the blood of every individual with hEDS and HSD. This fragment was notably absent in healthy controls, individuals with other types of EDS, and those with various kinds of arthritis. Additionally, a fragment of collagen I was found in all individuals with hEDS and HSD, although this fragment was also present in other conditions. The consistent presence of the 52 kDa fibronectin fragment in individuals with hEDS and HSD suggests a possible common underlying pathophysiology, thus questioning the differentiation between these conditions.

The research team used Western blotting to analyze plasma samples for fragments of connective tissue proteins. They compared participants with hEDS and HSD to 150 healthy controls, 10 people with classical EDS, 12 with vascular EDS, 40 with rheumatoid arthritis, 40 with psoriatic arthritis, and 40 with osteoarthritis. None of the healthy controls had any of these fragments in their blood, and only the participants with hEDS or HSD had the 52 kDa fibronectin fragment.

Key Findings

• Fibronectin and Collagen Fragments: The study found that people with hEDS and HSD shared the same pattern of fibronectin and collagen fragments in their blood, with the 52 kDa fibronectin fragment being unique to individuals with hEDS and HSD.
• Differentiation from Other Conditions: The study also identified specific fragments associated with osteoarthritis, rheumatoid arthritis, and psoriatic arthritis, which could help in diagnosis of these conditions.

Implications

• Potential Blood Test: The identification of these fragments could lead to the development of the first blood test for hEDS and HSD, providing a more reliable diagnostic tool for healthcare providers.
• Improved Diagnosis and Treatment: This biomarker could help reduce the time to diagnosis, which currently averages around 12 years, and improve treatment strategies for those affected by these conditions.

Future Research

The study’s findings are a significant step forward, but the authors emphasize that before this test is ready for diagnostic use, other investigators must confirm the results in additional cohorts of hEDS, HSD, and controls. The Ehlers-Danlos Society is sponsoring further confirmatory work. Currently, no diagnostic lab offers this test, but if validated, it could become an important tool in diagnosis and treatment trials and provide new insights into the underlying causes of hEDS and HSD.

Study Participants

Of the 466 individuals studied, 381 were recruited at the University of Brescia, Italy, and 85 were recruited from the USA by The Ehlers-Danlos Society. The study population included 154 females and 20 males with hEDS and HSD.

Frequently Asked Questions (FAQs)

1. 1. Did this study identify a genetic variant associated with hEDS?
      No, this study did not investigate the genetic cause(s) of hypermobile Ehlers-Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD). Instead, it focused on finding other biomarkers that could potentially be used to confirm a diagnosis of hEDS and HSD.
   2. What is a biomarker?
      A biomarker is something that can be measured in our blood, other body fluids, or tissues that is a sign of a condition or disease. There are many types of biomarkers, such as genetic biomarkers, immunological biomarkers, and changes in connective tissue proteins.
      This study identified a protein biomarker that may be associated with hEDS and HSD. It was found that study participants with hEDS and HSD had a specific fragment, or piece, of the fibronectin protein in their blood.
   3. What is a fragment?
      In this study, a fragment is a specific piece of a protein. Researchers looked for fragments of fibronectin, type I collagen, and tenascin proteins in the blood samples of study participants.
   4. What is a western blot?
      A western blot is a laboratory test that separates and detects specific proteins in a sample. Proteins are separated based on their size.
      Using a western blot test, this study identified a 52 KDa fragment (piece) of the fibronectin protein in the blood of people with hEDS and HSD.
   5. What does 52 kDa mean?
      KDa is a unit commonly used to measure the mass of proteins. The fibronectin protein fragment identified in the study weighed 52 kDa.
   6. How specific is the biomarker to hEDS and HSD? Could it be present in other conditions?
      The fibronectin biomarker was found in all 94 participants diagnosed with hEDS and 80 with HSD. None of the 150 healthy controls, 10 people with classical EDS, 12 with vascular EDS, 40 with rheumatoid arthritis, 40 with psoriatic arthritis, or 40 with osteoarthritis were found to have this protein fragment in their blood. This suggests that the biomarker appears specific to hEDS and HSD, but further research is needed to confirm this finding. Studies need to show that the findings can be repeated in other labs and also show that the fragment is not present in other conditions like fibromyalgia and ME/CFS or in healthy people with joint hypermobility.
   7. Can my doctor test me for this? When can we expect a test to be available?
      No, the development of a blood test will require further research and validation studies. If those studies validate the findings, it may take several years before such a test is widely available in clinical settings.
   8. How does this new biomarker compare to existing diagnostic methods for hEDS and HSD?
      This biomarker has the potential to offer a more accurate, objective, and reliable diagnosis compared to the current clinical criteria.
   9. What are the implications of this biomarker for patients who are already diagnosed with hEDS or HSD?
      For those already diagnosed, this biomarker might provide confirmation of their diagnosis or offer additional insights into their condition.
   10. Are there any limitations to using biomarkers in diagnosing hEDS and HSD?
       As with any diagnostic tool, there could be limitations. Factors such as variability in individual patients or the presence of the biomarker in other conditions could affect the accuracy of the test.
   11. How could this biomarker influence the future of hEDS and HSD treatment
       If validated, this biomarker could lead to more personalized treatment approaches, potentially allowing healthcare providers to tailor therapies based on the specific biological characteristics of the patient.
   12. Will this biomarker help in differentiating between hEDS and HSD?
       The study suggests that hEDS and HSD might share common biological characteristics, supporting the idea that they could be part of a spectrum rather than entirely separate conditions.
   13. Is this related to the HEDGE study? Is this related to the Norris Lab’s research?
       No, this study is separate from both the HEDGE study and the Norris Lab’s research.
   14. How can I get involved in future research?
       You can join the DICE EDS and HSD Global Registry to contribute to future research.

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

https://doi.org/10.1002/ajmg.a.63857