Antibody Blood Tests May Help Monitor Long-term Clinical Status
Lower levels of antibodies targeting acetylcholine receptors in the bloodstream of people with myasthenia gravis (MG) were associated with improved clinical status, a study demonstrated.
These findings showed not only that antibody blood tests are useful for diagnosing MG, but also that repetitive testing may be “valuable as a long-term monitor for clinical improvement in MG patients,” according to researchers.
Testing antibody levels “could possibly support clinicians in their decisions regarding continuing or changing immunosuppressive treatment,” they wrote.
The study, “The association between anti-acetylcholine receptor antibody level and clinical improvement in myasthenia gravis,” was published in the European Journal of Neurology.
The connection between nerves and the muscles they control is known as the neuromuscular junction. Here, nerve endings release a signaling molecule called acetylcholine, which binds to acetylcholine receptors (AChRs) on the surface of muscle cells, causing them to contract.
In MG, the immune system mistakenly generates antibodies, called autoantibodies, that target and damage AChRs and other components of the neuromuscular junction, causing muscle weakness and fatigue.
Autoantibodies that selectively target AChRs are found in 90% of people with generalized MG, a more widespread form of the disease that affects several muscle groups, and 50% of those with ocular MG — a form of MG in which muscles that control the eye and eyelid movements are the only ones affected.
Anti-AChR antibodies also are found in most MG patients with a thymoma — a tumor in the thymus, the gland in the chest where immune cells mature.
These anti-AChR antibodies found in the bloodstream are commonly used to confirm an MG diagnosis. However, due to conflicting evidence, there is no consensus regarding an association between autoantibody levels and a patient’s clinical status during the years of follow-up and treatment.
To investigate further, scientists at Maastricht University, in the Netherlands, designed a study to examine the utility of measuring anti-AChR-antibody levels. The goal was to determine if these levels would provide information about clinical status using the most accurate testing methods, a relevant follow-up period, and a large number of participants.
The team gathered medical records from adults with MG with more than one year of follow-up and two or more positive tests for anti-AChR antibodies (above 0.25 nanomole per liter of blood).
In total, 90 patients, ages 18–83, were included in the analysis, along with 837 blood test results.
Most participants were female (61.1%) and received immunosuppressive therapy (88.9%). Just over half (54.4%) had undergone a thymectomy, or surgery to remove the thymus.
More than half of the participants (58.8%) had an MGFA-symptom score at first assessment (baseline) matching MG class I — eye muscle weakness — or MG class II, demonstrating mild weakness in muscles other than those controlling eye movements. Of note, the Myasthenia Gravis Foundation of America (MGFA) score is a quantitative measure of disease severity for people with MG.
During the follow-up period, which ranged from 16 to 223 months (more than 18 years), 76 patients (84.4%) went into remission — meaning they ceased having symptoms — after two to 139 months (nearly 12 years).
“Although most patients did experience remission of MG during follow-up, this could take many months to years, and change in immunosuppressive therapy is no exception,” the team wrote.
The remaining 14 patients who did not go into remission were primarily female (64.3%), had received immunosuppressive therapy (64.3%), and did not have a thymoma (85.7%). These patients also were followed for a shorter period of time (46.4 vs. 85.8 months) compared with those who went into remission.
Among them, 40% showed increasing anti-AChR antibodies during follow-up, 46.7% had no change in antibody levels, and 13.3% saw their autoantibodies levels drop.
Statistical analysis found a significant inverse relationship between lower anti-AChR antibodies levels and the odds of symptom improvement. Specifically, every 10% decrease in autoantibody levels correlated with a 21% relative improvement in the MGFA scale. Similar results were seen after adjusting data for age, sex, immunosuppressive therapy use, thymectomy, and time since thymectomy.
“This indicates that repetitive measurements of [anti-AChR-antibody] serum levels can potentially be used to assist in the follow-up of a patient with MG,” the researchers wrote.
Thymectomy patients with a 10% decrease in autoantibody levels had a 15% increased odds of experiencing symptom improvement. There was a 45% increase in the odds of MGFA improvement for those who did not have surgery.
Patients who had their thymus surgically removed were often females (72%), younger than those who had not undergone a thymectomy (median age of 40.0 vs. 68.0 years), and experienced slower disease remission (median of 19 months vs. 11 months).
A comparison of baseline anti-AChR antibody levels with the next blood test taken between one and two years of follow-up showed a 10% decrease in autoantibody levels was associated with a 30% relative increase in the odds of MGFA improvement.
A final subgroup analysis explored the differences between fast- and slow-responders after starting immunosuppressive therapy. In one year, those who responded quickly to the medication saw their autoantibody levels drop by at least 50%. In contrast, slow-responders saw their autoantibody levels drop by less than 50% in two years.
Fast- and slow-responders significantly differed in age (median age of 63.0 vs. 53.0 years). In addition, slow-responders underwent a thymectomy more frequently than fast-responders (73.3% vs. 41.5%). There were no differences between the two groups in MG severity or autoantibody levels at baseline.
“These results indicate that the use of [anti-AChR-antibody] serum levels might be valuable as a long-term monitor for clinical improvement in MG patients,” the authors wrote, adding that data from such tests may help clinicians to better decide on continuing or changing immunosuppressive treatment.
“A future prospective study is necessary to provide additional information about the influence of different immunosuppressive strategies on [anti-AChR-antibody] serum levels to lead to more personalized treatment of patients with MG,” the researchers concluded.
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