5 blood proteins can tell MG from other autoimmune diseases: Study
Newly ID'd biomarkers able to diagnose rare condition, distinguish severity
- Five newly identified blood proteins — AXIN1, STAMBP, ST1A1, CDCP1, SIRT2 — can help distinguish myasthenia gravis from other autoimmune diseases.
- Other protein sets can indicate MG severity, age of onset, and treatment response.
- These blood biomarkers may help improve MG diagnosis, monitoring, and personalized treatment.
Blood levels of five proteins involved in the body’s inflammatory response may be used to diagnose myasthenia gravis (MG) and distinguish it from other autoimmune diseases, according to new research findings from scientists working in Sweden and Germany.
The research team also identified other small sets of inflammatory proteins able to help distinguish patient groups based on each individual’s age at MG onset, disease severity, and treatment status.
“This study validates the MG-specific [blood] … biomarkers AXIN1, STAMBP, ST1A1, CDCP1, and SIRT2 and identifies signatures associated with severity, onset, and treatment,” the researchers wrote.
While the role of these proteins in MG has yet to be understood, “these findings support the use of blood-based biomarkers for monitoring and stratification in MG clinical trials and care,” the team added.
Their study, “AXIN1, STAMBP, ST1A1, CDCP1, and SIRT2 Validated as Myasthenia Gravis Biomarkers: A Comparative Proteomic Study With MS, CIDP, and Controls,” was published in the European Journal of Neurology.
Scientists note lack of biomarkers specific to MG
MG occurs when self-reactive antibodies attack the neuromuscular junction — where nerves release signals for muscles to move — causing muscle weakness.
Diagnosing and managing the disease remains challenging, according to the researchers, because of a lack of MG-specific biomarkers.
“Current disease monitoring relies largely on clinical evaluations and subjective scales of muscle fatigability, which are insufficient to guide individualized treatment,” the researchers wrote. “Consequently, there is a growing need for objective, disease-specific biomarkers that can support longitudinal disease monitoring, patient stratification, and evaluation of therapeutic response.”
To test whether certain blood inflammatory proteins could fill that gap, the researchers analyzed blood samples from 200 adults with MG, who had a median age of 59. Nearly two-thirds (62.5%) were women. All carried self-reactive antibodies against the acetylcholine receptor protein, the most common MG-driving antibodies.
For comparison, the study also included 192 age- and sex-matched healthy adults, as well as 144 similarly matched adults diagnosed with one of two other autoimmune diseases. Among those individuals, 93 had multiple sclerosis and 51 had been diagnosed with chronic inflammatory demyelinating polyneuropathy, known as CIDP.
“We aimed to validate [blood] inflammatory proteins as potential biomarkers for MG, with a focus on their disease specificity and relevance for future treatment monitoring,” the researchers wrote.
To compare protein signatures, the team used a high-throughput test that quantifies many proteins at once.
A total of 14 proteins were found to differ between MG and healthy controls. Of these, five could distinguish MG not only from healthy controls but also from the two other autoimmune diseases: AXIN1, STAMBP, ST1A1, CDCP1, and SIRT2.
Disease severity was measured using the Myasthenia Gravis Foundation of America (MGFA) clinical scale, which groups patients based on the degree to which MG affects their daily function.
Of 185 patients, 29 were in remission, meaning their symptoms had eased or disappeared; 31 had ocular MG, with symptoms limited to the eyes (MGFA I); 110 had mild generalized weakness (MGFA II); and 15 had moderate generalized disease (MGFA III).
CDCP1 among ‘top 5’ blood proteins linked to MG severity
Blood levels of 15 proteins were significantly associated with MG severity. The researchers noted that CDCP1, as well as FGF-23, IL-24, CXCL9, and osteoprotegerin (OPG), “were the top five distinguishing proteins, with significantly higher levels in mild and moderate generalized MG compared to remission and ocular MG.”
According to the team, “this suggests a distinct inflammatory profile associated with disease progression, where these biomarkers may reflect heightened immune activation and inflammation in more severe MG subtypes.”
Levels of CDCP1, FGF-23, OPG, and other proteins were also significantly associated with other standard MG severity scores, “supporting their potential relevance as biomarkers of disease severity in MG,” the researchers wrote.
These biomarkers may reflect heightened immune activation and inflammation in more severe MG subtypes.
Another set of 28 proteins could distinguish patients based on the age at which their symptoms first appeared: This ranged from early onset to late and very late onset. Blood levels of several proteins, including CDCP1 and OPG, were greater with age at onset, while those of TRANCE and TWEAK proteins dropped with increasing age.
These proteins helped to distinguish early-onset MG — when symptoms begin before the age of 50 — from late-onset MG (between ages 50 and 65) and very late-onset MG (at 65 or older).
There was also a protein pattern in patients using immunosuppressants that was marked by lower levels of CD6 and TRANCE, and high Flt3L levels. Also, those treated with newer therapies — such as off-label rituximab and the approved therapy Vyvgart (efgartigimod) — had lower levels of CDCP1 and TNFRSF9.
“The identification of MG subgroup-specific biomarkers and treatment-associated protein changes provides new insights into disease [underlying mechanisms] and reveals potential targets for therapeutic monitoring,” the team wrote, noting that, among the study’s strengths, were its inclusion of a large number of patients alongside healthy controls and those with other autoimmune conditions.
“These findings advance the development of objective, blood-based biomarkers for MG, with implications for diagnosis, stratification, and personalized treatment. Future studies are needed to elucidate the functional roles of these proteins,” the researchers concluded.
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