Immunoglobulins from animal models of motor neuron disease and from human amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction.
Amyotrophic lateral sclerosis (ALS) is a devastating human disease of upper and lower motoneurons of unknown etiology. In support of the potential role of autoimmunity in ALS, two immune-mediated animal models of motoneuron disease have been developed that resemble ALS with respect to the loss of motoneurons, the presence of IgG within motoneurons and at the neuromuscular junction, and with respect to altered physiology of the motor nerve terminal. To provide direct evidence for the primary role of humoral immunity, passive transfer with immunoglobulins from the two animal models and human ALS was carried out. Mice injected with serum or immunoglobulins from the animal disease models and human ALS but not controls demonstrated IgG in motoneurons and at the neuromuscular junction. The mice also demonstrated an increase in miniature end-plate potential (mepp) frequency, with normal amplitude and time course and normal resting membrane potential, indicating an increased resting quantal release of acetylcholine from the nerve terminal. The ability to transfer motoneuron dysfunction with serum immunoglobulins provides evidence for autoimmune mechanisms in the pathogenesis of both the animal models and human ALS.
Appel
S H
SH
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
Engelhardt
J I
JI
García
J
J
Stefani
E
E
D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology* / Q000503:physiopathology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D004594:Electrophysiology / Q000379:methods; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology* / Q000302:isolation & purification; D016219:Immunotherapy, Adoptive; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009045:Motor Endplate / Q000502:physiology; D009046:Motor Neurons / Q000276:immunology* / Q000502:physiology; D009468:Neuromuscular Diseases / Q000276:immunology* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000502:physiology*; D012016:Reference Values
D007136:Immunoglobulins