Clinical and pathophysiologic relevance of autoantibodies in neonatal myasthenia gravis

Between 10% and 20% of neonates born to mothers with myasthenia gravis (MG) develop neonatal MG due to the transfer of maternal autoantibodies across the placenta. Neonatal MG can occur in infants born not only from mothers with acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) antibodies but also from mothers without detectable muscle antibodies. The low incidence rate may be due to specific autoantibody characteristics that differ among individuals, but a genetic predisposition in some infants is possible. The majority of reported neonatal MG cases are anti-AChR antibody-positive (AChR-MG), and a high anti-fetal/anti-adult AChR titer ratio in the mother is predictive of its occurrence. However, patients with anti-MuSK antibody-positive MG (MuSK-MG) are more likely to experience exacerbations during pregnancy and have a higher probability of developing neonatal MG than AChR-MG patients. Moreover, maternal MuSK-MG may be associated with early-onset and more severe manifestations of neonatal MG. Although cholinesterase inhibitors have been effectively used for treating neonatal AChR-MG, neonatal MuSK-MG may be more difficult to treat with this type of medication. Maternal MuSK-MG usually greatly benefits from intravenous immunoglobulin (IVIG) and plasma exchange. In neonatal MG, IVIG is considered for severely affected infants with MuSK-MG, but the efficacy of IVIG remains unclear. Although exchange transfusion may be a management adjunct, its clinical benefits are controversial. As the therapy-induced reduction of autoantibodies may be advantageous for fetal outcomes, maternal MG should be effectively treated during pregnancy. However, caution of drug contraindication during pregnancy and lactation must be exercised to avoid unwanted effects for the fetus and neonate. In the future, MG caused by anti-lipoprotein receptor-related protein 4 or other antibodies might be also identified in pregnant women and neonates. Therefore, the determination of autoantibody specificity is essential for successful management.