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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    ABSTRACT: Antibodies to a ganglioside complex consisting of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) are found in sera from patients with Guillain-Barré syndrome (GBS). To elucidate the clinical significance of anti-GM1/GalNAc-GD1a antibodies in GBS, clinical features of 58 GBS patients with IgG anti-GM1/GalNAc-GD1a antibodies confirmed by enzyme-linked immunosorbent assay and thin layer chromatography immunostaining were analyzed. Compared to GBS patients without anti-GM1/GalNAc-GD1a antibodies, anti-GM1/GalNAc-GD1a-positive patients more frequently had a preceding respiratory infection (n = 38, 66%, p < 0.01) and were characterized by infrequency of cranial nerve deficits (n = 9, 16%, p < 0.01) and sensory disturbances (n = 26, 45%, p < 0.01). Of the 28 anti-GM1/GalNAc-GD1a-positive patients for whom electrophysiological data were available, 14 had conduction blocks (CBs) at intermediate segments of motor nerves, which were not followed by evident remyelination. Eight of 10 bedridden cases were able to walk independently within one month after the nadir. These results show that the presence of anti-GM1/GalNAc-GD1a antibodies correlated with pure motor GBS characterized by antecedent respiratory infection, fewer cranial nerve deficits, and CBs at intermediate sites of motor nerves. The CB may be generated through alteration of the regulatory function of sodium channels in the nodal axolemma.
    Journal of Neuroimmunology 01/2013; 254(1-2):141-145. DOI:10.1016/j.jneuroim.2012.09.005 · 2.79 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.
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