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: A P Heikema, B C Jacobs, D Horst-Kreft, R Huizinga, M L Kuijf, H P Endtz, J N Samsom, W J B van Wamel
• Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (Clin Microbiol Infect) Vol. 19 Issue 2 Pg. E106-12 (Feb 2013) ISSN: 1469-0691 [Electronic] England
• PMID: 23173866 (Publication Type: Journal Article)
• Copyright: © 2012 The Authors Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Chemical References

• Antigens, Bacterial
• Antigens, Differentiation, Myelomonocytic
• Autoantibodies
• Lectins
• SIGLEC7 protein, human
• Sialic Acids

Topics

• Antigens, Bacterial (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Autoantibodies (blood)
• Campylobacter jejuni (chemistry, genetics, pathogenicity)
• Gene Knockout Techniques
• Guillain-Barre Syndrome (immunology, pathology)
• Humans
• Lectins (metabolism)
• Oculomotor Muscles (physiopathology)
• Protein Binding
• Sialic Acids (metabolism)