Intravenous immunoglobulin (IVIg) treatment improves mus- cle strength in Lambert-Eaton myasthenic syndrome (LEMS), butits specific mod e of action is unknown. We have delineated its mode of action on neuromuscular b ...Intravenous immunoglobulin (IVIg) treatment improves mus- cle strength in Lambert-Eaton myasthenic syndrome (LEMS), butits specific mod e of action is unknown. We have delineated its mode of action on neuromuscular b locking properties of LEMS IgG. The effect of sera and purified IgG from six pat ients with LEMS on evoked quantal release was investigated after direct applicat ion to the motor nerve terminal by the perfused macro-patch-clamp electrode in mouse hemidiaphragms. The effect of LEMS IgG was analyzed alone and after coinc ubation with different concentrations of IVIg or its Fab fragments. All LEMS ser a and purified LEMS IgG fractions taken before IVIg treatment inhibited evoked q uantal release in a dose-dependent manner. When LEMS IgG was coincubated with a therapeutic IVIg preparation, presynaptic inhibitory activity of LEMS IgG was d iminished in a dose-dependent fashion. Monovalent Fab fragments were as effecti ve in neutralizing the activity of LEMS IgG as whole IVIg. These direct neutrali zing effects of IVIg may explain its therapeutic efficacy.展开更多
文摘Intravenous immunoglobulin (IVIg) treatment improves mus- cle strength in Lambert-Eaton myasthenic syndrome (LEMS), butits specific mod e of action is unknown. We have delineated its mode of action on neuromuscular b locking properties of LEMS IgG. The effect of sera and purified IgG from six pat ients with LEMS on evoked quantal release was investigated after direct applicat ion to the motor nerve terminal by the perfused macro-patch-clamp electrode in mouse hemidiaphragms. The effect of LEMS IgG was analyzed alone and after coinc ubation with different concentrations of IVIg or its Fab fragments. All LEMS ser a and purified LEMS IgG fractions taken before IVIg treatment inhibited evoked q uantal release in a dose-dependent manner. When LEMS IgG was coincubated with a therapeutic IVIg preparation, presynaptic inhibitory activity of LEMS IgG was d iminished in a dose-dependent fashion. Monovalent Fab fragments were as effecti ve in neutralizing the activity of LEMS IgG as whole IVIg. These direct neutrali zing effects of IVIg may explain its therapeutic efficacy.
