Topology and patch-clamp analysis of the sodium channel in relationship to the anti-lipid a antibody in campylobacteriosis.
An infecting strain VLA2/18 of Campylobacter jejuni was obtained from an individual with campylobacteriosis and used to prepare chicken sera by experimental infection to investigate the role of serum anti-ganglioside antibodies in Guillain-Barré syndrome. Both sera of the patient and chicken contained anti-ganglioside antibodies and anti-Lipid A (anti-Kdo2-Lipid A) antibodies directed against the lipid A portion of the bacterial lipooligosaccharide. The anti-Kdo2-Lipid A activities inhibited voltage-gated Na (Nav) channel of NSC-34 cells in culture. We hypothesized that anti-Kdo2-Lipid A antibody acts on the functional inhibition of Nav1.4. To test this possibility, a rabbit peptide antibody (anti-Nav1.4 pAb) against a 19-mer peptide (KELKDNHILNHVGLTDGPR) on the alpha subunit of Nav1.4 was produced. Anti-Nav1.4 pAb was cross-reactive to Kdo2-Lipid A. Anti-Kdo2-lipid A antibody activity in the chicken serum was tested for the Na(+) current inhibition in NSC-34 cells in combination with mu-Conotoxin and tetrodotoxin. Contrary to our expectations, the anti-Kdo2-Lipid A antibody activity was extended to Nav channels other than Nav1.4. By overlapping structural analysis, it was found that there might be multiple peptide epitopes containing certain dipeptides showing a structural similarity with v-Lipid A. Thus, our study suggests the possibility that there are multiple epitopic peptides on the extracellular domains of Nav1.1 to 1.9, and some of them may represent target sites for anti-Kdo2-Lipid A antibody, to induce neurophysiological changes in GBS by disrupting the normal function of the Nav channels.
Usuki
Seigo
S
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912-2697, USA.
Nakatani
Yoshihiko
Y
Taguchi
Kyoji
K
Fujita
Tetsuhiro
T
Tanabe
Shinya
S
Ustunomiya
Iku
I
Gu
Yihua
Y
Cawthraw
Shaun A
SA
Newell
Diane G
DG
Pajaniappan
Mohanasundari
M
Thompson
Stuart A
SA
Ariga
Toshio
T
Yu
Robert K
RK
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015153:Blotting, Western; D002169:Campylobacter Infections / Q000276:immunology*; D016123:Campylobacter jejuni / Q000276:immunology*; D002645:Chickens; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008050:Lipid A / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000276:immunology; D020033:Protein Isoforms / Q000276:immunology; D015222:Sodium Channels / Q000737:chemistry / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D005732:Gangliosides; D008050:Lipid A; D010455:Peptides; D020033:Protein Isoforms; D015222:Sodium Channels