Novel anti-idiotype antibody therapy for lipooligosaccharide-induced experimental autoimmune neuritis: use relevant to Guillain-Barré syndrome.
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.
Usuki
S
S
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912-2697, USA.
Taguchi
K
K
Thompson
S A
SA
Chapman
P B
PB
Yu
R K
RK
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D019921:Biotinylation / Q000379:methods; D016123:Campylobacter jejuni / Q000276:immunology; D018920:Coculture Techniques / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D051638:Ether-A-Go-Go Potassium Channels / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D008070:Lipopolysaccharides; D009046:Motor Neurons / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications / Q000276:immunology / Q000628:therapy*; D020511:Neuromuscular Junction Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D045442:Rotarod Performance Test / Q000379:methods; D012584:Sciatic Nerve / Q000473:pathology / Q000648:ultrastructure; D013116:Spinal Cord / Q000502:physiology; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D051638:Ether-A-Go-Go Potassium Channels; D005732:Gangliosides; C485664:Kcnh4 protein, rat; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; C023023:lipid-linked oligosaccharides; C026226:ganglioside, GD3; D005620:Freund's Adjuvant