Molecular mechanisms associated with impaired peripheral nerve repair mediated by anti-ganglioside antibodies

CRISTIAN BACAGLIO; BERARDO ANDRES; BARBARA BAEZ; VIVINETTO ANA L; MATTALLONI, M.S.; PABLO H H LOPEZ

Simposio; 3er Simposio Argentino de Glicobiología: GlycoAR 2019; 2019

Guillain Barré Syndrome (GBS) is an acute monophasic polyneuropathy characterized by the presence of ascending muscular paralysis and arreflexia. In a subgroup of patients, paralysis is related to the presence of high titers of antibodies targeting gangliosides (anti-Gg). Passive transfer studies with a mAb anti-Gg (anti GD1a-GT1b, clone 1b7) in a murine model of axon regeneration confirmed that these antibodies are able to inhibit nerve repair by negative modulation of actin and tubulin cytoskeleton in growth cones. However, recent findings in this model show that nerves from animals exposed to anti-Gg display a significant failure in the clearance of tissue debris, suggesting a possible effect on non-neural cells. Preliminary in experiments display that mice treated with mAb 1B7 show a reduced number of macrophage extravasation/migration in sciatic nerves respect to control nerves. Furthermore, in vivo experiments highlight a role of anti-Gg in the modulation of macrophage phenotype. Circulating macrophages and sciatic nerve extravased macrophages showed a M2 like phenotype in mice treated with anti-Gg compared with control, measured by qPCR and inmunofluorescence. In conclusion, these results suggest effect of anti-Gg on nerve repair by targeting non-neural cells.