AChR Autoantibodies Reflect Disease Severity, Study Indicates

Beyond being a diagnostic tool, antibodies against acetylcholine receptors (AChR) in the blood reflect disease severity and could be a useful biomarker for myasthenia gravis (MG) progression, a study suggested.

The findings also indicated that a blood protein called C5a may help identify patients with more severe disease.

The study, “C3, C5a and anti-acetylcholine receptor antibody as severity biomarkers in myasthenia gravis,” was published in the journal Therapeutic Advances in Neurological Disorders. 

Most MG cases are caused by autoantibodies — those targeting the body’s own tissues — against AChR at the neuromuscular junction, where nerve cells communicate with muscles. The result is the activation of the complement system, a set of more than 30 blood proteins that are part of the immune system, which impairs signaling between nerves and muscles.

Despite evidence of complement system components in the neuromuscular junction of people with MG, no markers of clinical severity are available. Also, although anti-AChR antibodies are useful to diagnose patients, whether the levels of these antibodies can be used to measure disease severity is still unclear. 

To find out, researchers at the University of Buenos Aires, in Argentina, measure the levels of anti-AChR antibodies in 60 adults with generalized MG and investigated the relationship with clinical severity. The team also measured the levels of immune complement proteins known as C3, C4, and C5a. 

The study included 39 women and 21 men, ages 20 to 88 years, with disease onset between the ages of 3 and 82 years. Median MG duration was nine years. A group of 49 healthy individuals of similar sex and age was included as controls.

Information regarding thymus abnormalities, history of thymus removal, and types of treatments received also was collected. Almost a quarter of the participants (23%) had had their thymus removed (thymectomy).

Patients underwent a neurological examination using the activities of daily living (ADL) scale and the MG composite (MGC) scale. Based on assessments, patients were divided into those with active (exacerbated) or stable disease. 

Results revealed that higher anti-AChR antibodies levels in blood correlated more severe disease as assessed by ADL and MGC, with a trend toward higher concentrations in exacerbated MG patients than in those with stable disease (5.9 vs. 4.7 nanomol/L). 

In patients who had experienced symptoms for less than five years, the scientists found that anti-AChR antibodies levels correlated with clinical severity. In this group, those with higher levels of such antibodies had more severe disease. Also in this group, the team found a trend toward lower levels of C3 and higher levels of C5 in people with higher clinical severity on the ADL scale. 

Participants with early-onset disease showed lower levels of C3 and C4. In contrast, no associations were identified between either complement protein and anti-AChR antibodies, as well as between all tested biomarkers and gender, thymus abnormalities, or thymus removal. 

As for treatment, the concentrations of both anti-AChR antibodies and C5a were higher in patients receiving immunosuppressive therapies such as CellCept (mycophenolate mofetil) than in those taking Mestinon (pyridostigmine) only.

Finally, a detailed evaluation of different treatment combinations found a trend between higher levels of C5a and greater clinical severity in patients who received azathioprine and corticosteroids. 

“In conclusion, the present study demonstrates that AChR-[antibody levels] may be a useful marker of disease severity regardless of the adopted treatment and serum [blood] complement levels,” the scientists wrote.

“C5a concentration was higher in patients with more severe MG, however, there were no differences in levels between patients and healthy controls. So C5a is a nonspecific marker in patients with MG,” they added. “Further studies are necessary in order to confirm the usefulness of complement factors as a biomarker of MG.”