Antibody levels may help track disease severity in children with MG

Most children with juvenile myasthenia gravis (JMG) develop mild disease marked by eye muscle weakness, with more severe symptoms seen in those who are older when they start showing signs of disease, according to a single-center study in China.

Data also suggested that blood levels of self-reactive antibodies against anti-acetylcholine receptor (AChR) proteins — the most common type of antibody driving myasthenia gravis (MG) — may help predict JMG severity and relapse risk, offering potential guidance for patient prognosis and management.

“The complexity of the initial symptoms in [JMG] patients is related to increasing age,” the researchers wrote. “Interestingly, [anti-AChR antibody] levels may be a potential factor in predicting patient prognosis.”

The study, “Clinical Characteristics of childhood-onset Myasthenia Gravis in a Large Chinese Cohort,” was published in Pediatric Neurology.

MG is usually caused by self-reactive antibodies that target proteins involved in nerve-muscle communication, typically AChRs, leading to MG symptoms such as muscle weakness and fatigue. JMG affects children and adolescents up to age 18. Rates vary between regions, being reported in up to 15% in Caucasian population and 50% in some Chinese studies.

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Exploring variations in clinical characteristics

“The clinical characteristics and demographics of [JMG] patients vary significantly between regions and ethnic groups,” the researchers wrote.

To learn more about the clinical characteristics of JMG in China, they retrospectively analyzed clinical data from 1,031 children and adolescents with JMG who were treated at a single specialized center from 2013 to 2023.

Participants had a median age at disease onset of 5. Most were girls (58.2% ), and 1.7% had a family history of MG.

Overall, 62.4% of the children and adolescents had anti-AChR antibodies, while 0.5% had antibodies targeting muscle-specific kinase, the second most common target of MG-driving antibodies. More than a third (37.25%) tested negative for either antibody.

Most patients (90.4%) had ocular MG, in which the disease affects only the muscles in and around the eyes, while 9.6% had generalized MG, in which weakness had spread to muscles other than those related to the eyes.

Participants were divided by age at disease onset into three groups: 3 and younger, 4-10, and older than 10.

Weakness in eye muscles was the most common initial symptom across all age groups, present in 93.2% of the children. Rates of initial eye muscle weakness were higher in the two younger groups than in the older group (94.1%-98.1% vs. 78.8%), while the older group had a significantly higher rate of initial muscle weakness affecting the limbs (13.5% vs. 0.7%-3.6%) and face, neck, and/or throat (5.9% vs. 1%-1.8%).

Across all age groups, most children were classified as Myasthenia Gravis Foundation of America (MGFA) class 1, the mildest category of disease severity, defined by eye-related muscle weakness alone.

The frequency of mildest disease was highest in the youngest age group, while those older than 10 had the highest incidence of severe disease affecting muscles other than those in the eyes (MGFA classes 4 and 5).

There were no significant differences among age groups in coexisting conditions, family history, the presence and type of self-reactive antibodies, or relapse rates, with a median follow-up time of three years.

Further statistical analyses showed that children with MGFA class 1 and those with ocular MG had significantly lower blood levels of anti-AChR antibodies than those with MGFA class 2 and those with generalized MG. Follow-up data demonstrated that anti-AChR antibody levels were highest among patients with relapsing disease.

“The severity of initial symptoms in [JMG] patients was related to age and we found that the [anti-AChR antibody level] was associated with MGFA classification grade and prognosis,” the researchers wrote.

The researchers said they plan to conduct a future study following patients over longer periods, analyze different treatment interventions, and collect more comprehensive data “to further investigate the impact of these factors on the long-term prognosis of [JMG] patients.”