Passive transfer of IgG anti-GM1 antibodies impairs peripheral nerve repair.
Anti-GM1 antibodies are present in some patients with autoimmune neurological disorders. These antibodies are most frequently associated with acute immune neuropathy called Guillain-Barré syndrome (GBS). Some clinical studies associate the presence of these antibodies with poor recovery in GBS. The patients with incomplete recovery have failure of nerve repair, particularly axon regeneration. Our previous work indicates that monoclonal antibodies can inhibit axon regeneration by engaging cell surface gangliosides (Lehmann et al., 2007). We asked whether passive transfer of human anti-GM1 antibodies from patients with GBS modulate axon regeneration in an animal model. Human anti-GM1 antibodies were compared with other GM1 ligands, cholera toxin B subunit and a monoclonal anti-GM1 antibody. Our results show that patient derived anti-GM1 antibodies and cholera toxin beta subunit impair axon regeneration/repair after PNS injury in mice. Comparative studies indicated that the antibody/ligand-mediated inhibition of axon regeneration is dependent on antibody/ligand characteristics such as affinity-avidity and fine specificity. These data indicate that circulating immune effectors such as human autoantibodies, which are exogenous to the nervous system, can modulate axon regeneration/nerve repair in autoimmune neurological disorders such as GBS.
Lopez
Pablo H
PH
Department of Neurology, The Johns Hopkins University, Baltimore, Maryland 21287, USA.
Zhang
Gang
G
Zhang
Jiangyang
J
Lehmann
Helmar C
HC
Griffin
John W
JW
Schnaar
Ronald L
RL
Sheikh
Kazim A
KA
D000704:Analysis of Variance; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D004594:Electrophysiology; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D009416:Nerve Regeneration / Q000276:immunology*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D005732:Gangliosides; C048844:anti-IgG