Anti-ganglioside antibodies alter presynaptic release and calcium influx.
Acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome is often associated with IgG anti-GM1 and -GD1a antibodies. The pathophysiological basis of antibody-mediated selective motor nerve dysfunction remains unclear. We investigated the effects of IgG anti-GM1 and -GD1a monoclonal antibodies (mAbs) on neuromuscular transmission and calcium influx in hemidiaphragm preparations and in cultured neurons, respectively, to elucidate mechanisms of Ab-mediated muscle weakness. Anti-GM1 and -GD1a mAbs depressed evoked quantal release to a significant yet different extent, without affecting postsynaptic currents. At equivalent concentrations, anti-GD1b, -GT1b, or sham mAbs did not affect neuromuscular transmission. At fourfold higher concentration, an anti-GD1b mAb (specificity described in immune sensory neuropathies) induced completely reversible blockade. In neuronal cultures, anti-GM1 and -GD1a mAbs significantly reduced depolarization-induced calcium influx. In conclusion, different anti-ganglioside mAbs induce distinct effects on presynaptic transmitter release by reducing calcium influx, suggesting that this is one mechanism of antibody-mediated muscle weakness in AMAN.
Buchwald
Brigitte
B
Research Group Neurophysiology, Section Neurology, Max-Planck-Institute of Psychiatry, Munich, Germany.
Zhang
Gang
G
Vogt-Eisele
Angela K
AK
Zhang
Weiyi
W
Ahangari
Raheleh
R
Griffin
John W
JW
Hatt
Hanns
H
Toyka
Klaus V
KV
Sheikh
Kazim A
KA
D000818:Animals; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology; D002118:Calcium; D002478:Cells, Cultured; D003964:Diaphragm / Q000276:immunology / Q000378:metabolism; D005732:Gangliosides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009469:Neuromuscular Junction / Q000276:immunology / Q000502:physiology; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009830:Olfactory Bulb; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000276:immunology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D005732:Gangliosides; D018377:Neurotransmitter Agents; D002118:Calcium