Molecular mimicry: sensitization of Lewis rats with Campylobacter jejuni lipopolysaccharides induces formation of antibody toward GD3 ganglioside.
Recently we have reported cases of demyelinating inflammatory neuropathy showing elevated titers of anti-GD3 antibodies, which occurs rarely in Guillain-Barré syndrome. To examine the correlation between the anti-GD3 antibody titer and Campylobacter jejuni infection, we sensitized female Lewis rats with lipopolysaccharides (LPSs) from serotype HS19 of C. jejuni and examined changes in nerve conduction velocity and nerve conduction block (P/D ratio). After 16 weeks of sensitization, animals revealed decreases of nerve conduction velocity and conduction block (P/D ratio) and high titer of anti-GD3 antibodies. These anti-GD3 antibodies also blocked transmission in neuromuscular junctions of spinal cord-muscle cells cocultures. The GD3 epitope was verified to be located on the Schwann cell surface and nodes of Ranvier in rat sciatic nerve. To determine the target epitope for GD3 antibodies in causing nerve dysfunction, the LPS fraction containing the GD3 epitope was purified from the total LPS by using an anti-GD3 monoclonal antibody-immobilized affinity column. Subsequently, chemical analysis of the oligosaccharide portion was performed and confirmed the presence of a GD3-like epitope as having the following tetrasaccharide structure: NeuAcalpha2-8NeuAc2-3Galbeta1-4Hep. Our data thus support the possibility of a contribution of GD3 mimicry as a potential pathogenic mechanism of peripheral nerve dysfunction.
Usuki
Seigo
S
Institute of Molecular Medicine and Genetics and Institute of Neuroscience, Medical College of Georgia, Augusta, Georgia 30912-2697, USA.
Thompson
Stuart A
SA
Rivner
Michael H
MH
Taguchi
Kyoji
K
Shibata
Keiko
K
Ariga
Toshio
T
Yu
Robert K
RK
D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D016123:Campylobacter jejuni / Q000737:chemistry / Q000276:immunology*; D002855:Chromatography, Thin Layer / Q000379:methods; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography / Q000379:methods; D000939:Epitopes; D005071:Evoked Potentials / Q000502:physiology / Q000528:radiation effects; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000378:metabolism; D007163:Immunosorbent Techniques; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D018716:Molecular Mimicry / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew / Q000276:immunology*; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D013997:Time Factors; D017186:Titrimetry / Q000379:methods
D000939:Epitopes; D005732:Gangliosides; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D016900:Neurofilament Proteins; C026226:ganglioside, GD3