[Pathogenic antibodies in myasthenia gravis].
Myasthenia gravis (MG) is the most common autoimmune disorder of the neuromuscular junction and is clinically characterized by weakness and muscle fatigue. We have classified MG into 3 types on the basis of the antibody pattern. The first type associated with acetylcholine receptor (AChR) autoantibodies, which predominantly belong to IgG1 subclass and are measured by a conventional radioimmunoprecipitation assay with 125I-alpha-bungarotoxin. This subtype occurs in approximately 80% of patients with MG and leads to the loss of AChR number and function, mainly by complement-mediated destruction of the neuromuscular junction. Approximately 40% of patients with MG who have AChR antibodes have a thymoma as a paraneoplastic neurological syndrome. However, the role of antigen expression by thymomas is unclear. The second type of MG occurs in a proportion of "seronegative" patients who did not have AChR autoantibodies. These patients process IgG autoantibodies to muscle-specific tyrosine kinase (MuSK); these antibodies are predominantly of the IgG4 subclass but are not associated with complement-mediated damage to the neuromuscular junction or with the presence of thymomas. In most patients with MuSK antibodies, the symptoms of MG improve after plasma exchange; these patients show a good response to steroid and immunosuppressive drugs but a poor response to thymectomy. MG not associated with the presence of the 2 abovementioned pathogenic autoantibodies is classified as heterogeneous "double seronegative" MG. Our classification is superior to the present classifications with regard to the mechanism, treatment, and prognosis of the disease.
Motomura
Masakatsu
M
First Department of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
D001323:Autoantibodies; D006801:Humans; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009157:Myasthenia Gravis / Q000276:immunology / Q000628:therapy; D009469:Neuromuscular Junction; D020361:Paraneoplastic Syndromes, Nervous System; D010951:Plasma Exchange; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011950:Receptors, Cholinergic; D011505:Protein-Tyrosine Kinases