Antibodies to Ganglioside Complexes in Guillain-Barré Syndrome: Clinical Correlates, Fine Specificity and Complement Activation

Abstract

In the Schwann cells and neuronal plasma membranes the gangliosides are organized in clusters forming complexes of gangliosides in the microdomains termed lipid rafts. We investigated frequency, clinical correlates, fine specificity and pro-inflammatory properties of antibodies to ganglioside complexes (GSCs) in a Guillain Barre syndrome (GBS) population. In 63 patients with different GBS variants we performed an ELISA for antibodies to Campylobacter Jejuni (C. jejuni), gangliosides and GSCs. We studied the fine specificity of antibodies to GSCs by immunoabsorption study and performed a complement activation assay. Twenty-seven percent of patients had antibodies to GSCs and 71 percent had antibodies either to single gangliosides or to GSCs. Patients with antibodies to GSCs had more frequent involvement of cranial nerves but did not present more frequent antecedent respiratory, gastrointestinal or C. jejuni infection, did not have a preferential demyelinating or primary axonal GBS variant and did not develop greater disability at six months. The absorption study showed in 2 sera that antibodies to the complex GD1a/GD1b did not react with the gangliosides forming the complex or other single gangliosides, suggesting that antibodies to GSCs are targeted to new conformational glycoepitopes different from the ones displayed by the single gangliosides. Antibody anti-GSCs activated the complement more frequently than antibodies to single gangliosides. Complement activation indicates that antibodies to GSCs have high avidity, pro-inflammatory properties and may exert a pathogenic role in GBS.

Antiganglioside antibodies are associated with axonal Guillain–Barré syndrome: A Japanese–Italian collaborative study

“…There are some possibilities for this discrepancy. Firstly, the target molecules involved in AMAN are not only GM1 but also GM1b, GD1a, GalNAc-GD1a or ganglioside complexes 23 24. Other unidentified gangliosides could also be targets for autoantibodies in AMAN.…”

Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

“…For instance, another form of GBS called Miller-Fisher syndrome is characterized by antibodies against ganglioside GQ1b [115]. More recently, it has been shown that autoantibodies in a small number of GBS patients recognize complexes formed by two different gangliosides, for instance GD1a/GD1b and GD1a/GM1 [116, 117]. This knowledge has improved anti-ganglioside antibody detection rates and led to reclassification of a small number of patients who were seronegative for autoantibodies against individual gangliosides [116].…”

Autoantibodies to neurofascin-186 and gliomedin in multifocal motor neuropathy

“…Complement activation by purified antibodies to NF186 and gliomedin was determined, as previously described (Notturno et al, 2009), using microtiter plates (Polysorp Nunc; Roskilde, DK) coated with 0.5 μg/well of gliomedin and NF186. Bead elution fractions obtained from non-coated beads and bead elution fractions obtained from neurofascin and gliomedin coated beads were incubated overnight at 4°C; wells coated with a concentration range of purified human IgG (Sigma-Aldrich; 100-0.1 μg/ml) and BSA (1% in PBS) were used as positive and negative controls, respectively.…”

“…Bead elution fractions obtained from non-coated beads and bead elution fractions obtained from neurofascin and gliomedin coated beads were incubated overnight at 4°C; wells coated with a concentration range of purified human IgG (Sigma-Aldrich; 100-0.1 μg/ml) and BSA (1% in PBS) were used as positive and negative controls, respectively. Complement activation has been considered positive if OD was greater than media + 2 SD control sera OD (Notturno et al, 2009). …”