Antibody Status Predicts Remission in Juvenile Myasthenia Gravis, Study Suggests

The type of antibodies found in children with myasthenia gravis (MG) was the primary predictor of disease remission, or not requiring medication for one full year, a study showed. 

Additional factors influencing remission were being younger than 10 years old at disease onset, Asian and Caucasian backgrounds, a lack of AChR antibodies, and normal results from repetitive nerve stimulation (RNS) tests at diagnosis. 

The study, “Paediatric myasthenia gravis: Prognostic factors for drug free remission,” was published in the journal Neuromuscular Disorders.

Myasthenia gravis is an autoimmune disorder in which antibodies, normally produced to fight infection, target receptors found at the junction between nerve endings and muscles (neuromuscular junction). 

Some antibodies attack the acetylcholine receptor (AChR) directly, while others target different proteins that support AChR function such as muscle-specific kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4). There also is a group of MG patients known as seronegative, meaning they test negative to all antibodies. 

MG typically occurs in adults. Information on clinical outcomes, antibody types, and predictors of MG in children, called juvenile MG (or JMG), is limited. 

Researchers based at two hospitals in the U.K. — John Radcliffe Hospital in Oxford and Great Ormond Street Hospital for Children in London — conducted an analysis of the medical records of juvenile MG patients to examine clinical outcomes, neurological findings, and antibody subtypes, and to identify clinical predictors of JMG.

The team selected 74 patients diagnosed with JMG with symptom onset before the age of 16 who were evaluated at either hospital between 2007 and 2018. The patient group was multi-ethnic, with 52% being non-Caucasian.

Information was collected regarding antibodies’ types and standard tests for abnormal neuromuscular transmission such as RNS or single-fiber electromyography were performed. 

The severity of JMG was classified according to the Myasthenia Gravis Foundation of America clinical classification at maximum level. JMG outcome was measured by the Scale of Millichap and Dodge, in which the lowest level was remission without medication for one full year, followed by a good response requiring medication, then a moderate response at high medication dosage, then no change or worsening and, at the highest level, death.

The analysis found disease-associated antibodies in 66 of the 74 patients (89%). Of these, 62 patients had AChR antibodies, three had MuSK antibodies, and one had antibodies targeting LRP4. A total of 60 patients had neurophysiological testing, 45 of whom showed abnormal neuromuscular function. The number whose eyes were affected was 38 (51%). 

Treatment was given to 70 of the 74 patients and included cholinesterase inhibitors to increase the amount of acetylcholine at the neuromuscular junction, an anti-inflammatory steroid (prednisolone), regular infusions of therapeutic antibodies, plasma exchange, or immunosuppressants. 

Remission — without medication for one year —was achieved in 17 (23%) of the patients, and 25% reached complete remission in seven years. For this group, the follow-up time was more than two years. 

Of the 57 children who did not achieve remission, 32 (42%) had a good response to medications, 14 (19%) had a moderate response with high dosage, and 12 (16%) did not improve despite medication. There were no deaths reported. 

The factors found to be associated with remission were patient’s age of less than 10 years at disease onset, Asian or Caucasian ethnicity, a lack of AChR antibodies from standard tests, and a normal RNS at diagnosis. 

A more detailed statistical analysis found that antibody status was the only significant predictor of remission. The patients who achieved remission were either seronegative or had AChR antibodies, found by a non-standard, more sensitive cell-based test.

“Complete drug free remission is not uncommon in paediatric MG and several factors appear to influence this outcome with antibody status being the most important,” the scientists said. “These factors can be easily evaluated at diagnosis, and may help to determine whose patients are likely to require more intensive treatments.”