Passively transferred Lambert-Eaton syndrome in mice receiving purified IgG.

Abstract

Purified IgG antibodies were prepared by ion-exchange chromatography from the plasma of a patient with nonneoplastic form of the Lambert-Eaton myasthenic syndrome (LES). The antibodies were injected into mice with daily doses of 0.15-10 mg for 20-22 days, following which the integrity of neuromuscular transmission was assessed in vitro in phrenic nerve-diaphragm muscle preparations. The injected animals manifested electrophysiologic features of human LES, which were characterized by: dose-dependent reduction in the quantal content of nerve-evoked endplate potentials, an abnormally small increase in the frequency of spontaneous miniature endplate potentials (MEPPs) with elevated [K+]o, and normal MEPP amplitude with no evidence of postjunctional deficiency. Crude immunoglobulins (Igs) from the same patient and two LES patients with associated malignancy similarly transferred the defects in quantal transmitter release. In contrast, animals receiving Igs from control subjects or from a patient with small-cell carcinoma of the lung manifested no functional impairment of neuromuscular transmission. Instead, the evoked release in these animals was significantly enhanced relative to that found in normal untreated mice. These results suggest that an IgG antibody produces the presynaptic impairment that is characteristic of LES and support the concept that LES with and without cancer has an autoimmune pathogenesis.