Antibodies in Myasthenia Gravis and Related Disorders

Myasthenia gravis (MG) is caused in the majority of cases by circulating autoantibodies to the nicotinic muscle acetylcholine receptor (AChR). Several studies have now documented a higher incidence of AChR-positive MG in both men and women over age 60 years than among younger individuals (Vincent et al. JNNP in press). Since MG can be misdiagnosed as stroke or motor neuron disease in the elderly, it is likely that there is considerable underdiagnosis of MG in this age group. Fetal AChR antibodies and arthrogryposis maternal antibodies to the fetal isoform of the AChR are found in rare cases of arthrogryposis multiplex congenital. They cross the placenta and cause paralysis in the developing fetus leading to joint contractures and other deformities. Seronegative myasthenia gravis antibodies to AChRs are present in about 85% of patients with generalized disease. Antibodies to the muscle specific receptor tyrosine kinase, MuSK, are found in 0–70% of SNMG patients; those with MuSK antibodies often present with predominant ocular and bulbar weakness, or neck extensor weakness, and may be more difficult to treat effectively with conventional immunosuppression (Vincent et al. Lancet Reviews Neurology 2002). Plasma or serum from SNMG patients may also inhibit the function of AChR expressed on TE671 cells, or on the subline that expresses adult AChRs. The effect appears to be indirect, perhaps acting on another muscle surface receptor that activates a second messenger system leading to reduced AChR function. This plasma factor is not an IgG and co-purifies with IgM (Plested et al. Neurology 2002), and its target is unknown. Voltage-gated ion channels and CNS disease antibodies to the voltage-gated calcium and potassium channels are found in Lambert Eaton myasthenic syndrome and acquired neuromyotonia, respectively. Recently, we have detected very high levels of VGKC antibodies in an increasing number of patients with „limbic“ encephalitis. Many do not have evidence of peripheral neuromuscular involvement but show high signal intensity in the temporal lobe(s), seizure activity and low plasma sodium levels. These patients, who typically do not have an associated tumor, may do well after long-term immunosuppression (Vincent et al. Brain 2004).