title: Human IgM paraproteins demonstrate shared reactivity between Campylobacter jejuni lipopolysaccharides and human peripheral nerve disialylated gangliosides.
abstract: IgM paraproteins from patients with CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein, agglutination, anti-disialosyl antibodies) react with NeuAc(alpha 2-8)NeuAc epitopes on a wide range of gangliosides including GQ1b, GT1a, GD1b and GD3. The tissue distribution of reactive antigens in human peripheral nerve has not been addressed in detail. In addition, the origin of these antibodies is unknown. Here we report that purified anti-disialosyl paraproteins from two affected patients bind a wide array of human peripheral nerve structures including dorsal root ganglia, dorsal and ventral root axons, femoral and oculomotor nerves. We also show that these paraproteins bind lipopolysaccharides of Campylobacter jejuni isolates from 3/3 cases of Miller Fisher syndrome, and to a less frequent extent, from cases of Guillain-Barré syndrome and enteritis controls. In conjunction with our previous studies, these data provide a possible causal link between the origin and pathogenic effects of anti-disialosyl antibodies in human paraproteinaemic neuropathy.
authors.affiliation: Department of Neurology, Erasmus University, Rotterdam, The Netherlands.
authors.forename: B C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: G M
authors.initials: GM
authors.lastname: O'Hanlon
authors.forename: E G
authors.initials: EG
authors.lastname: Breedland
authors.forename: J
authors.initials: J
authors.lastname: Veitch
authors.forename: P A
authors.initials: PA
authors.lastname: van Doorn
authors.forename: H J
authors.initials: HJ
authors.lastname: Willison
mesh_terms: D000371:Agglutination; D001259:Ataxia / Q000276:immunology / Q000378:metabolism; D016123:Campylobacter jejuni / Q000378:metabolism*; D002908:Chronic Disease; D064211:Connectin; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D019085:Fluorescent Antibody Technique, Direct; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009124:Muscle Proteins; D009194:Myeloma Proteins / Q000032:analysis; D009886:Ophthalmoplegia / Q000276:immunology / Q000378:metabolism; D010266:Paraproteins / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D064211:Connectin; D005732:Gangliosides; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D009194:Myeloma Proteins; D010266:Paraproteins; D012794:Sialic Acids; C085016:multiple myeloma M-proteins