New Biomarker Research Could Help in Diagnosing HSD & hEDS
The Ehlers-Danlos Society recently shared updates in research regarding blood-based biomarkers that could potentially be used in diagnosing hypermobility spectrum disorders (HSD) and hypermobile Ehler-Danlos syndrome (hEDS).
Historically, hEDS has been the only subtype of Ehlers-Danlos syndrome to not have a genetic marker that could be used in diagnostic studies to identify the syndrome. This is groundbreaking for those seeking treatment and are unsure if they have either syndrome.
For further context, laboratory testing has been minuscule until recent years for hypermobility disorders. Only a few labs, such as The Norris Lab located in Charleston, South Carolina, have dedicated studies to hypermobile EDS. With The Ehlers-Danlos Society’s funding through their “Molecular Studies in hEDS and HSD Grants” this study was able to be conducted.
The study was conducted by collecting blood samples from 466 adults. 94 of these were individuals diagnosed with hEDS, and 80 were diagnosed with HSD. The sample was made up of 150 healthy controls, 10 with classical EDS, 12 with vascular EDS, and 120 people with the various forms of arthritis. The population included 154 females and 20 males with HSD and hEDS. A potential reason for more females in the study is because women tend to be more symptomatic and seek treatment than males.
The two nationalities studied were Italian and American. The Ehlers-Danlos Society enrolled participants from the USA, and most participants were found through three outpatient clinics in Brescia, Italy.
The average age of the hEDS Italian participants was 38.4 years old, with an age range of 18 to 68 years old. The average age of the hEDS American participants was 37.9 years old, with an age range of 22 to 71 years old.
When looking specifically at HSD participants, the average age for Italian participants was 36.7 years old, when a range of 18 to 72 years old. For American HSD participants, the average age was 39.5 years old, with a range of 22 to 52 years old.
Western blotting techniques were used to analyze the plasma samples, focusing on connective tissue proteins. Collagen I was found in hEDS and HSD participants, but also found in those with other conditions. The team also found the presence of a specific 52 kDA fragment of fibronectin.
When comparing blood samples, no one except the individuals with hEDS or HSD had the 52 kDa fragment of fibronectin.
What could this mean?
Well, the research also located fragments that could be associated with psoriatic arthritis, osteoarthritis, and rheumatoid arthritis. These could be beneficial in the diagnosis and treatment of these conditions as well.
For those with hypermobility conditions such as hEDS & HSD, this could give them the potential development of the first-ever blood test for the conditions.
Rather than relying solely on symptomatic diagnostic sheets, there could be lab work that actually shows the potential presence of the condition. It is still several years out before this would be available in most clinical settings.
It could also provide evidence toward the argument that hEDS diagnostic criteria needs to be revised, since the 52 kDA fragment was seen in participants that failed to meet criterion one or two. There are arguments that criterion one is restrictive, and that criterion two includes insufficient multisystemic clinical signs and symptoms.
Criterion one, according to the International Consortium on Ehlers-Danlos Syndroms & Related Disorders, details generalized joint hybermobility through Beighton Score, with various requirements based on age. Criterion two has three sets of features, with two or more of the groups being required to be present. These groups include various features spanning from dental crowing to having a mitral valve prolapse.
A goal of many researchers is to provide research to aid in the restructuring of classification framework for EDS and its many subtypes.
This could also decrease the wait for a diagnosis, which is typically around twelve years currently. Now that there is a specific protein that can be located, treatment options may be developed with further research.
Individuality still plays a role, however, and this fragment may not be seen in everyone. Other conditions could potentially affect the accuracy of the test. On a positive note, individualized and personalized treatment approaches could be developed with the biological characteristics of patients.
Another suggestion of this study is that HSD and hEDS may share similar biological characteristics, supporting the concept of a spectrum of hypermobility rather than separate conditions. Someone may be double-jointed and flexible, but that does not necessarily mean they have HSD or hEDS.
Flexibility is a spectrum, as is hypermobility.
More research must be conducted first before the test can be validated as a diagnostic resource. The test must be conducted again with more groups of subjects with hEDS and HSD. Thankfully, The Ehlers-Danlos Society is planning to support testing to confirm the work through recreating the study.
For further reading, check out the original 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,” at https://doi.org/10.1002/ajmg.a.63857.
