Abstract
Myasthenia is caused by abnormalities in signal transduction at the neuromuscular junction. Its pathophysiology which is broadly classified into acquired myasthenia gravis and congenital myasthenic syndrome has been elucidated and its treatment has progressed over the past half century. Childhood-onset myasthenia gravis is less common than adult-onset myasthenia gravis, and therefore the pathophysiology has not been well studied, and treatment has continued to be based on research in the adult setting. However, treatment of children should be based on an understanding of their pathophysiology, and research on pathophysiology and treatment methods that take into account their unique growth and development is desired. In recent years, studies on myasthenia have been reported from around the world, confirming that the pattern of the number of patients by age of onset differs between East Asia and Western Europe, and that the Japanese characteristic of a high incidence in childhood is widely seen in East Asia. Furthermore, differences in the incidence of congenital myasthenic syndrome between East Asia and Western Europe are also evident. Thus, there are racial differences in the pathophysiology of myasthenia based on genetic background, and their pathophysiology and relevance are gradually becoming clear.
Congenital myasthenic syndrome is caused by genetic defects in various proteins involved in the assembly of AChRs at the neuromuscular junction, resulting in impaired neuromuscular signaling and the appearance of myasthenic symptoms. On the other hand, myasthenia gravis which is a T cell-dependent, antibody-producing autoimmune disease, is caused by autoantibodies against several proteins, mainly AChR antibodies. These proteins, like congenital myasthenic syndrome, are involved in the assembly of AChRs at the neuromuscular junction. Autoantibodies to these proteins prevent the assembly of AChRs, resulting in myasthenic symptoms due to the inability of neuromuscular signaling.
The ocular muscle type, which is common not only in Japan but also in East Asia, has low antibody titers and seronegative MG is relatively common. In this review, I would like to summarize and discuss what is happening at the neuromuscular junction in myasthenia, especially the pathophysiology of myasthenia gravis with low antibody titers from various viewpoints, such as the presence of antibodies to neuromuscular junction proteins, the inability to measure antibody titers due to measurement sensitivity issues, diversity by muscle site or type, or involvement of cellular immunity.