title: Siglec-7 specifically recognizes Campylobacter jejuni strains associated with oculomotor weakness in Guillain-Barré syndrome and Miller Fisher syndrome.
abstract: Due to molecular mimicry, Campylobacter jejuni lipo-oligosaccharides can induce a cross-reactive antibody response to nerve gangliosides, which leads to Guillain-Barré syndrome (GBS). Cross-reactive antibodies to ganglioside GQ1b are strongly associated with oculomotor weakness in GBS and its variant, Miller Fisher syndrome (MFS). Antigen recognition is a crucial first step in the induction of a cross-reactive antibody response, and it has been shown that GQ1b-like epitopes expressed on the surface of C. jejuni are recognized by sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7). We aimed to determine the epitope specificity of C. jejuni binding to Siglec-7, and correlate the outcome to disease symptoms in GBS and MFS patients. Using a well-defined GBS/MFS-associated C. jejuni strain collection, which included three sialic acid knockout strains, we found that Siglec-7 exclusively binds to C. jejuni strains that express terminal disialylated ganglioside mimics. When serological and diagnostic patient records were correlated with the Siglec-7-binding properties, we observed an association between Siglec-7 binding and the presence of anti-GQ1b antibodies in patient serum. In addition, Siglec-7 binding was associated with oculomotor weakness in GBS and MFS patients. Lipo-oligosaccharide-specific binding of C. jejuni to Siglec-7 may be an initiating event in immune recognition and presentation, and lead to anti-GQ1b antibody production and the development of ocular weakness in GBS or MFS.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. a.heikema@erasmusmc.nl
authors.forename: A P
authors.initials: AP
authors.lastname: Heikema
authors.forename: B C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: D
authors.initials: D
authors.lastname: Horst-Kreft
authors.forename: R
authors.initials: R
authors.lastname: Huizinga
authors.forename: M L
authors.initials: ML
authors.lastname: Kuijf
authors.forename: H P
authors.initials: HP
authors.lastname: Endtz
authors.forename: J N
authors.initials: JN
authors.lastname: Samsom
authors.forename: W J B
authors.initials: WJ
authors.lastname: van Wamel
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood*; D016123:Campylobacter jejuni / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity*; D055786:Gene Knockout Techniques; D020275:Guillain-Barre Syndrome / Q000276:immunology / Q000473:pathology*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000503:physiopathology; D011485:Protein Binding; D012794:Sialic Acids / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D015214:Antigens, Differentiation, Myelomonocytic; D001323:Autoantibodies; D037102:Lectins; C402206:SIGLEC7 protein, human; D012794:Sialic Acids