Tissue-specific antibodies in myasthenia gravis.

Myasthenia gravis (MG) is a disorder of the neuromuscular junction characterised by weakness which increases on effort and is improved by rest and anticholinesterase treatment. Thymic abnormality with increased numbers of germinal centres is common, thymoma occurs in about 15% of cases, and thymectomy is often beneficial in thosewithoutatumour. The condition is commoner in women and typically becomes evident in early adult life. It can, however, present at any age, and there is a rare congenital form in which weakness dates from the neonatal period (see below). For a recent review see Drachman (1978). The main features of the normal and myasthenic neuromuscular junction are shown in Fig. 1. In MG the presynaptic nerve terminals are essentially normal although there is often elongation of the endplate with changes in the number of terminal expansions. There are, however, marked postsynaptic changes which include simplification of the postsynaptic membrane and loss of the secondary folds (Santa et al., 1972). These are associated with a decrease in the total number of acetylcholine receptors, as detected by oa-bungarotoxin binding (Fambrough et al., 1973), which are probably also reduced in number per unit area of postsynaptic membrane (Ito et al., 1978a). These changes are responsible for the underlying physiological defect in MG-namely, a pronounced reduction in the sensitivity to acetylcholine (ACh). As a result the effect of each packet or quantum of ACh (the miniature endplate potential) is reduced (Elmqvist et al., 1964) and the effect of nerve impulse-evoked release of 50 or so packets (the endplate potential) is insufficient to activate the muscle (for a fuller description, see Ito et al., 1978b).