Ganglioside complexes as new target antigens in Guillain-Barr� syndrome
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.
Journal of Neurology Neurosurgery & Psychiatry 02/2012; 83(3):e1-e1. DOI:10.1136/jnnp-2011-301993.23 · 5.58 Impact Factor
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ABSTRACT: Objective Enzyme-linked immunosorbent assay (ELISA) is the conventional technique for antiglycolipid antibody testing in inflammatory neuropathy sera. Miniaturized array-based assays (glycoarrays) have also been used to detect these antibodies. As previous studies have focused on specific disease categories, such as Guillain–Barré syndrome, the array has never been tested on an unselected population in a routine diagnostic laboratory setting.Methods In the present prospective study, we compared the results of the glycoarray with data obtained with a standardized inflammatory neuropathy cause and treatment-ELISA. A total of 300 sera sent to the Glasgow Neuroimmunology Laboratory for routine antiglycolipid antibody testing during a 6-month period were tested both with ELISA and glycoarray.ResultsThe two techniques were significantly correlated and showed good agreement. By ELISA, six sera were positive for immunoglobulin G antibodies against GM1 or GD1a, 11 for immunoglobulin G anti-GQ1b antibodies, five for immunoglobulin M anti-GM1 antibodies and three for immunoglobulin M antibodies against disialosyl gangliosides. The glycoarray had a sensitivity of 92% to detect ELISA-positive sera with a specificity above 92% for all the different ELISA patterns.Conclusions The glycoarray allows testing of large panels of antibodies against single glycolipids and complexes of glycolipids on a very small scale. Its technical characteristics make it suitable as a diagnostic screening test. As data provided by the glycoarray and ELISA were reliably correlated in the present study, the glycoarray can be used in a routine setting to detect antiglycolipid antibodies. Further studies, including more positive samples, are required to clarify the future position of the array in the biological investigation of inflammatory neuropathies.01/2015; DOI:10.1111/cen3.12193
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ABSTRACT: Recent studies have shown that antiganglioside antibody-mediated complement activation plays a key role in development of Guillain–Barré syndrome and related disorders. Additionally, complement-independent nerve dysfunction is suggested by in vitro studies, showing that antiganglioside antibodies directly inhibit voltage-gated Ca channel currents and change the integrity of lipid rafts. These pathogenic actions of antiganglioside antibodies might be governed by the avidity of the antibodies, which is influenced by specific localization of target gangliosides in the peripheral nervous system or glycolipid environment around the target antigens. The recent discovery of antibodies to ganglioside complexes has expedited the understanding of the mechanisms underlying antiganglioside antibody-mediated nerve dysfunction in Guillain–Barré syndrome and related disorders. In chronic immune-mediated neuropathy, some antiganglioside antibodies have also been identified as diagnostic markers, although their pathophysiological roles remain to be determined.06/2013; 4(1). DOI:10.1111/cen3.12007