Myasthenia gravis (MG) is hallmarked by acquired and fluctuating weakness of voluntary muscles. In the majority of patients, weakness is caused by autoantibodies to the postsynaptic acetylcholine... Show moreMyasthenia gravis (MG) is hallmarked by acquired and fluctuating weakness of voluntary muscles. In the majority of patients, weakness is caused by autoantibodies to the postsynaptic acetylcholine receptor (AChR) in the neuromuscular junction. Approximately 10% of MG patients are seronegative (SNMG). In 2001, antibodies to muscle-specific kinase (MuSK) were discovered within this group. This dissertation describes the epidemiology, clinical characteristics and immunological aspects of this new disease. In the Netherlands, MuSK MG is rare. Incidence was 0.17 per million person-years. Prevalence was 2.8 per million on January 1st 2004. Weakness was more often bulbar, and lead to frequent respiratory crises. MuSK MG was linked to the HLA-DR14-DQ5 haplotype and the disease severity was associated to antigen-specific IgG4 antibodies instead of IgG1. This is in contrast to AChR MG in which autoantibodies are mainly of the IgG1 and IgG3 subclass, and the disease is linked to HLA-B8-DR3. In SNMG patients, no antibodies to postsynaptic ErbB receptors were found. A case-report describes the transmission of MuSK autoantibodies from mother to her newborn child, causing transient weakness in the infant. A second case-report illustrates the effect of MuSK antibodies on both pre- and postsynaptic signal transmission in the neuromuscular junction. Show less
