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.
"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). "
[Show abstract][Hide abstract] 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; 268(1). DOI:10.1016/j.jneuroim.2014.01.012 · 2.47 Impact Factor
"In addition to serological reactions with single ganglioside or glycolipid species, it has recently been observed that certain GBS-associated autoantibodies may only bind to ganglioside complexes (GSC). GSC antibodies react with mixtures of two different gangliosides, whilst failing to recognise either component ganglioside alone, [12,13]. This concept builds on the long standing hypotheses of a lectin-binding “clustered saccharide patch” . "
[Show abstract][Hide abstract] ABSTRACT: Autoantibodies are infrequently detected in the sera of patients with the demyelinating form of Guillain-Barré syndrome most commonly encountered in the Western world, despite abundant circumstantial evidence suggesting their existence. We hypothesised that antibody specificities reliant on the cis interactions of neighbouring membrane glycolipids could explain this discrepancy, and would not have been detected by traditional serological assays using highly purified preparations of single gangliosides. To assess the frequency of glycolipid complex antibodies in a Western European cohort of patients GBS we used a newly developed combinatorial glycoarray methodology to screen against large range of antigens (11 gangliosides, 8 other single glycolipids and 162 heterodimeric glycolipid complexes). Serum samples of 181 patients from a geographically defined, Western European cohort of GBS cases were analysed, along with 161 control sera. Serum IgG binding to single gangliosides was observed in 80.0% of axonal GBS cases, but in only 11.8% of cases with demyelinating electrophysiology. The inclusion of glycolipid complexes increased the positivity rate in demyelinating disease to 62.4%. There were 40 antigens with statistically significantly increased binding intensities in GBS as compared to healthy control sera. Of these, 7 complex antigens and 1 single ganglioside also produced statistically significantly increased binding intensities in GBS versus neurological disease controls. The detection of antibodies against specific complexes was associated with particular clinical features including disease severity, requirement for mechanical ventilation, and axonal electrophysiology. This study demonstrates that while antibodies against single gangliosides are often found in cases with axonal-type electrophysiology, antibodies against glycolipid complexes predominate in cases with demyelinating electrophysiology, providing a more robust serum biomarker than has ever been previously available for such cases. This work confirms the activation of the humoral immune system in the dysimmune disease process in GBS, and correlates patterns of antigen recognition with different clinical features.
PLoS ONE 12/2013; 8(12):e82337. DOI:10.1371/journal.pone.0082337 · 3.23 Impact Factor
"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). "
[Show abstract][Hide abstract] 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 · 2.47 Impact Factor
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