Autor(es)Buchwald Brigitte,Zhang Gang,Vogt-Eisele Angela K,Zhang Weiyi,Ahangari Raheleh,Griffin John W,Hatt Hanns,Toyka Klaus V,Sheikh Kazim A

ResumoAcute 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.

ImprentaNeurobiology of Disease, v. 28, n. 1, p. 113-121, 2007

DescritoresGuillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Transmission ; Guillain-Barre Syndrome - Immunology

Data de Publicação:2007