Ganglioside complexes as new target antigens in Guillain-Barr� syndrome

Kinki University, Ōsaka, Ōsaka, Japan
Annals of Neurology (Impact Factor: 11.91). 10/2004; 56(4):567-71. DOI: 10.1002/ana.20222
Source: PubMed

ABSTRACT Antibodies specific for a complex of gangliosides GD1a and GD1b (GD1a/GD1b) were found in sera from eight of 100 patients with Guillain-Barre syndrome (GBS) by the use of enzyme-linked immunosorbent assay and thin-layer chromatogram immunostaining. Those sera also had antibody activities to such ganglioside complexes as GD1a/GM1, GD1b/GT1b, and GM1/GT1b but had little or no reactivity to the each isolated antigen. Clustered epitopes of the ganglioside complex in the plasma membrane may be targeted by such an antibody, and interaction between the antibody and ganglioside complex may induce the neuropathy.

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    • "IgM antibodies against gangliosides, glycolipids that are abundantly expressed in peripheral nerves, are target antigens in some patients with IgM-PNP without anti-MAG antibodies, but prevalence and antibody specificities of these antibodies have only been studied in relatively small groups of patients (Eurelings et al., 2001; Nobile-Orazio et al., 2010; Larue et al., 2011). More recently, antibodies that bind complexes of more than one ganglioside have been identified in patients with Guillain–Barré syndrome (GBS) and chronic immune-mediated neuropathies including one patient with IgM-PNP (Kaida et al., 2004, 2006; Hamaguchi et al., 2007; Kaida et al., 2007, 2008; Kanzaki et al., 2008; Kusunoki et al., 2008; Notturno et al., 2009; Ogawa et al., 2009; Nobile-Orazio et al., 2010) and could represent important additional target antigens in patients with IgM-PNP (Comi et al., 2002). We therefore investigated the presence of antibodies against single gangliosides and their complexes in sera from 54 patients without anti-MAG antibodies from a prospective cohort of 140 patients with polyneuropathy associated with IgM gammopathy (Niermeijer et al., 2010). "
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    ABSTRACT: IgM antibodies against gangliosides and their complexes were studied in sera from 54 patients with polyneuropathy and IgM monoclonal gammopathy (IgM-PNP) without anti-MAG antibodies. Anti-ganglioside antibodies were found in 19 (35%) patients. Five (9%) patients had antibodies against ganglioside complexes. IgM antibodies against gangliosides activated complement in vitro. Light chain usage was restricted to kappa or lambda in most, but not all patients. In conclusion, anti-ganglioside antibodies in IgM-PNP are common, display pathogenic properties and do not always arise from a monoclonal B cell proliferation.
    Journal of neuroimmunology 03/2014; DOI:10.1016/j.jneuroim.2014.01.012 · 2.79 Impact Factor
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    • "Guillain–Barre syndrome (GBS) is considered as an acute, immunemediated polyradiculoneuropathy having different clinical phenotypes arising after minor viral or bacterial infections, vaccination or surgery. Approximately 60% of patients with GBS have autoantibodies to specific epitopes present on gangliosides in the myelin sheath (Kusunoki et al., 1996; Willison and Yuki, 2002) and/or ganglioside complexes (Kaida et al., 2004). Immune responses directed towards gangliosides and their microbial mimics (bacterial or viral) are the only known mediators of this post-infection acute inflammatory polyradiculoneuropathy (Yuki, 2001). "
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    ABSTRACT: Guillain-Barre syndrome (GBS) is considered as an acute, immune-mediated polyradiculoneuropathy with different clinical phenotypes arising after viral or bacterial infections, vaccination or surgery. However, in 40% of GBS patients the aetiology remains unknown. In this manuscript, we report the occurrence of GBS in a patient bitten by a snake (Vipera aspis) for which a cross-reaction was shown between GM2 ganglioside and glycosidic epitopes of venom proteins. The venom of the snake implied in the patient's envenomation was collected. Its composition was characterised by ELISA and SELDI-TOF MS. Cross-reactivities between venom proteins and GM2 gangliosides were identified by Western blot after immunoabsorption of patient's serum with increasing amounts of purified GM2. Enzymatic deglycosylation of the venom was performed to determine the specificity of the patient's serum cross-reaction. We proved the absence of neurotoxicity of the viper venom. The patient's serum presented specific cross-reactions with several glycosylated venom proteins. After deglycolysation of these proteins, the patient's serum cross-reactivity was abolished. Furthermore, we compared the immune response to venom proteins of sera from two groups of patients. The first group showed IgM reactivity against GM2 ganglioside associated with GBS, and cross-reacted with venom proteins. The second group presented an IgM reactivity against CMV, without neurological disorders, and reacted with neither venom proteins nor gangliosides. Our study proved the auto-immunological aetiology of GBS in our patient based on molecular mimicry mechanisms between venom proteins and GM2 ganglioside.
    Journal of neuroimmunology 12/2011; 242(1-2):72-7. DOI:10.1016/j.jneuroim.2011.11.007 · 2.79 Impact Factor
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    • "In another case of ''clustered saccharide patches,'' antibodies may recognize and bind to a complex of two or more sialylated glycans but fail to bind the individual sialoglycans. For example, patients with Guillain Barré or Miller Fisher syndrome produce antibodies specific for ganglioside complexes, including GQ1b/GM1 and GQ1b/GD1a, but which do not bind to the single isolated gangliosides (Kaida et al., 2004; Kanzaki et al., 2008). Sialome recognition at this level of complexity may be analyzed using combinatorial glycoarrays , an array of heterodimeric mixtures of gangliosides compared with single ganglioside (Rinaldi et al., 2009). "
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    ABSTRACT: The glycome is defined as the glycan repertoire of cells, tissues, and organisms, as found under specified conditions. The vastly diverse glycome is generated by a nontemplate driven biosynthesis, which is indirectly encoded in the genome, and very dynamic. Due to this overwhelming diversity, glycomic analysis must be approached at different hierarchical levels of complexity. In this review five such levels of complexity and the experimental approaches used for analysis at each level are discussed for a subclass of the glycome: the sialome. The sialome, in analogy to the canopy of a forest, covers the cell membrane with diverse array of complex sialylated structures. Sialome complexity includes modification of sialic acid core structure (the leaves and flowers), the linkage to the underlying sugar (the stems), the identity, and arrangement of the underlying glycans (the branches), the structural attributes of the underlying glycans (the trees), and finally, the spatial organization of the sialoglycans in relation to components of the intact cell surface (the forest). Understanding the full complexity of the sialome thus requires combined analyses at multiple levels, that is, the sialome is far more than the sum of its parts.
    Omics: a journal of integrative biology 08/2010; 14(4):455-64. DOI:10.1089/omi.2009.0148 · 2.73 Impact Factor
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