| Abstract: |
Campylobacteriosis is a frequent antecedent event in Guillain-Barré syndrome (GBS), inducing high-titer serum antibodies for ganglioside antigens in the peripheral nervous system (PNS). Molecular mimicry between the lipooligosaccharide (LOS) component of Campylobacter jejuni and human peripheral nerve gangliosides is believed to play an important role in the pathogenesis of GBS. Conventional treatment strategies for patients with GBS include plasmapheresis, intravenous immunoglobulin (IVIG), and immunosuppression, which are invasive or relatively ineffective. In this study, we used our animal model of GBS, in which Lewis rats were immunized with GD3-like LOS isolated from C. jejuni. The animals developed anti-GD3 ganglioside antibodies and manifested neuromuscular dysfunction. To develop novel therapeutic strategies, we treated the animals by intraperitoneal administration of an anti-GD3 antiidiotype monoclonal antibody (BEC2) that specifically interacts with the pathogenic antibody. The treated animals had a remarkable reduction of anti-GD3 antibody titers and improvement of motor nerve functions. The results suggest that ganglioside mimics, such as antiidiotype antibodies, may be powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic antiganglioside antibodies. © 2010 Wiley-Liss, Inc. |
| Keywords: |
immunohistochemistry; controlled study; unclassified drug; area under the curve; nonhuman; animal cell; animals; animal tissue; animal experiment; animal model; nerve tissue proteins; dose-response relationship, drug; morphology; time factors; monoclonal antibody; syndrome; nerve fiber; spinal cord; motor neurons; rat; rats; maximum plasma concentration; time to maximum plasma concentration; drug blood level; organ culture techniques; enzyme-linked immunosorbent assay; drug half life; disease models, animal; autoimmune disease; nerve function; neurologic disease; neuromuscular disease; biotinylation; motoneuron; immunization; muscle, skeletal; coculture techniques; gangliosides; ganglioside; drug purification; sciatic nerve; isolation procedure; neuromuscular synapse; anti-idiotype antibody; campylobacter jejuni; gd3 ganglioside; guillain-barré; lipooligosaccharide; ganglioside antibody; idiotypic antibody; monoclonal antibody bec2; autoimmune neuritis; guillain barre syndrome; motor nerve; neuritis; rotarod test; action potentials; antibodies, anti-idiotypic; ether-a-go-go potassium channels; freund's adjuvant; lipopolysaccharides; neuritis, autoimmune, experimental; neuromuscular junction diseases; rotarod performance test
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