Alpha-bungarotoxin blocking antibodies in neonatal myasthenia gravis: frequency and selectivity

We have studied antibodies to the acetylcholine receptor (AChR) that inhibit alpha-bungarotoxin binding in 22 mothers with myasthenia gravis (MG) and in their 23 newborns. Of the 13 showing neonatal MG, seven of the mothers had detectable direct blocking antibodies, all 13 had decamethonium-dependent (DC) blocking, and nine had high titres of precipitating antibodies (greater than 40 nM). In those with symptom-free newborns, the corresponding figures were 2/10, 8/10 and 2/10; the mean titres of DC blocking and of precipitating antibodies were 5- and 3-fold lower than in the mothers of affected babies. Thus, blocking antibodies, in addition to high total antibody levels, may help to predict the occurrence of neonatal MG. However, the antibodies appear not to cross the placenta to the same extent in each case. 86, 69 and 84% of the maternal antibodies with precipitating, direct and DC blocking activities, respectively, were found in the myasthenic neonates versus 65, 28 and 44% in the unaffected. These data suggest (1) involvement of blocking antibodies in the pathogenesis of MG, and (2) variable placental transfer of anti-AChR antibodies, which makes neonatal affliction more difficult to predict.