The Pathophysiological Role of Anti-Ganglioside Antibodies in Peripheral Nervous System Disorders

Paparounas, Konstantinos E (2001) The Pathophysiological Role of Anti-Ganglioside Antibodies in Peripheral Nervous System Disorders. PhD thesis, University of Glasgow.

Abstract

In this study we investigated the neurophysiological effects, as well as the binding properties and complement activating ability of neuropathy-associated human anti-ganglioside antisera and monoclonal antibodies on isolated nerves and nerve-muscle preparations. Two categories of antibodies were studied: anti-GM1 antisera and monoclonal antibodies from patients with chronic motor neuropathies and Guillain-Barre syndrome, and anti-GQ1b and related anti-disialosyl antisera and monoclonal antibodies from patients with chronic ataxic neuropathies and Miller Fisher syndrome. In vitro recordings for up to 4 hours of compound nerve action potentials, latencies, rise times and stimulus thresholds from isolated ensheathed and desheathed sciatic nerve and rabbit desheathed sural nerve as well as twitch tension from mouse phrenic nerve-hemidiaphragm preparation were performed, in the presence of anti-ganglioside antibodies and fresh human serum as an additional source of complement. No changes were observed over this time course, with all electrophysiological parameters being within 15% of the starting values for both normal and antibody containing sera. Immunohistological evaluation of desheathed nerves exposed to anti-ganglioside antibodies demonstrated antibody deposition with complement activation at up to 90% of nodes of Ranvier in some preparations. These data indicate that anti-ganglioside antibodies can diffuse into nerve, bind to nodes of Ranvier and fix complement in vitro without resulting in any acute physiological deterioration, suggesting that the node of Ranvier is relatively resistant to acute anti-ganglioside antibody mediated injury. The data also suggest that anti-ganglioside antibodies are unlikely to exert major direct pharmacological effects on nodal function and neuromuscular transmission. The models used in this study failed to give an in vitro approval of the suggested pathophysiological effects of anti-ganglioside antibodies on nerve and nerve-muscle function, possibly because their limited viability does not allow time for the evolution of a full inflammatory lesion, and in vivo models may be more suitable for identifying the effects of these antibodies on nerve conduction.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Hugh J Willson
• Keywords: Neurosciences
• Date of Award: 2001
• Depositing User: Enlighten Team
• Unique ID: glathesis:2001-76030
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Dec 2019 09:15
• Last Modified: 19 Dec 2019 09:15
• URI: https://theses.gla.ac.uk/id/eprint/76030