Fibronectin protein fragment may help diagnose hEDS/HSD: Study
Fragment appears to be found only in adults with 2 hypermobility diseases
A fragment of fibronectin, a protein that assists in wound healing, appears to be found only in the blood of adults with hypermobile Ehlers–Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD), a study found, suggesting it as a biomarker for diagnosis.
Because the fragment could not be detected in the blood of people with other joint diseases, the findings of this study could “[lay] the groundwork for developing … targeted diagnosis and treatment approaches, paving the way for improved patient care,” the researchers wrote.
“Exploring the therapeutic implications of targeting [such protein] fragments holds promise,” the team added.
The study, “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,” was published in the American Journal of Medical Genetics.
Investigating fragments of protein, including fibronectin, in blood
Both hEDS and HSD involve changes in the body’s connective tissues that manifest as overly elastic skin and hypermobile joints, or joints that move beyond the normal range of motion. Diagnosing hEDS and HSD is difficult because no single biomarker or laboratory test is available.
“Despite considerable research efforts over the years, the daunting reality remains: the absence of any available molecular basis or laboratory test makes the diagnosis and classification of these patients extremely challenging,” the researchers wrote.
Telling hEDS from HSD is also hard due to overlapping symptoms, a “diagnostic ambiguity [that] not only places a substantial burden on healthcare practitioners but also significantly impacts patients, leading to prolonged diagnostic journeys, misdiagnosis, and potentially harmful delays in appropriate management.”
The researchers already knew that hEDS and HSD involve changes in the extracellular matrix, a network of proteins that normally provides structure to the body’s tissues. In both hEDS and HSD, these proteins are disorganized and broken down into fragments that get released into the surrounding spaces.
Now, the 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.
All patients with hEDS or HSD showed a unique pattern with the presence of a 52 kDa fragment of fibronectin in the blood. This fragment was not detected in the blood of healthy people or patients with classical EDS, vascular EDS, or any of the three types of arthritis.
A fragment of collagen I, another protein that forms part of the extracellular matrix, was found in all patients with hEDS or HSD, although it was also present in blood samples from patients with rheumatoid arthritis.
Our study represents a significant advance by highlighting the potential of [blood] biomarkers to enhance diagnostic classification not only for hEDS/HSD but also for the investigated inflammatory and degenerative joint diseases, while expanding our understanding of molecular mechanisms.
The unique pattern of protein fragments of fibronectin and collagen I 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.
The findings could lead to the development of the first blood test for diagnosing hEDS and HSD, making it easier to identify and treat these diseases, according to the researchers. The results also may provide new insights into the causes of these two diseases and suggest ways to restore organization to the extracellular matrix.
“Our study represents a significant advance by highlighting the potential of [blood] biomarkers to enhance diagnostic classification not only for hEDS/HSD but also for the investigated inflammatory and degenerative joint diseases, while expanding our understanding of molecular mechanisms,” the researchers concluded.
The Ehlers-Danlos Society is now sponsoring confirmatory studies.
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