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Year : 2017  |  Volume : 65  |  Issue : 5  |  Page : 971--972

Guillian-Barre syndrome and variants: Antiganglioside antibodies

J M K Murthy 
 Department of Neurology, The Institute of Neurological Sciences, CARE Hospitals, Banjara Hills, Hyderabad, Telangana, India

Correspondence Address:
J M K Murthy
Department of Neurology, The Institute of Neurological Sciences, CARE Hospitals, Banjara Hills, Hyderabad, Telangana
India




How to cite this article:
Murthy J. Guillian-Barre syndrome and variants: Antiganglioside antibodies.Neurol India 2017;65:971-972


How to cite this URL:
Murthy J. Guillian-Barre syndrome and variants: Antiganglioside antibodies. Neurol India [serial online] 2017 [cited 2020 Apr 4 ];65:971-972
Available from: http://www.neurologyindia.com/text.asp?2017/65/5/971/214080


Full Text

Gangliosides are sialic acid-containing glycosphingolipids ubiquitous in human cell membranes, but particularly concentrated in the axolemma at the nodes of Ranvier and nerve terminals. About twenty different types of gangliosides have been identified differing in the number of relative position of the hexose and sialic acid residues.[12] The most commonly used nomenclature for the classification of gangliosides is that proposed by Svennerholm.[2],[3] According to this nomenclature, G stands for ganglio-series of ganglioside; M, D, T, and Q refer to the number of sialic acid moieties (mono-, di-, tri-, and quadri-, respectively). The Arabic numbers and the small letters refer to the sequence of migration as determined by thin layer chromatography.[2],[3],[4] Antibodies to antigens of myelin and axon are usually of polyclonal origin, but can be restricted to a single immunoglobulin class. Antibodies in peripheral neuropathy appear to recognize the glycolipid antigens rather than the protein antigens of myelin or axon.[4]

Guillian-Barre syndrome (GBS) is a heterogenous disorder and the spectrum includes: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and Miller Fisher Syndrome (MFS).[5] Bickerstaff brainstem encephalitis can also be considered a variety of GBS.[6] Acute motor-sensory axonal neuropathy (AMSAN) and acute motor conduction block neuropathy are likely the extreme forms of the AMAN. Some patients with MFS may develop quadriparesis (MFS-GBS overlap syndrome).[6] Antiganglioside IgG antibodies, GM1 and GD1a are associated with AMAN.[5] In the Japan-Italian Collaborative study, 83% of patients with AMAN had IgG antibodies to GM1, GD1a, or GM1b.[7] IgG antibodies to the ganglioside GQ1b are associated with MFS, MFS-GBS overlap syndrome and Bickerstaff brainstem encephalitis.[5] In the study by Naik et al.,[8] in this issue of Neurology India, antiganglioside antibodies were significantly positive in patients with AMAN. Of the 15 patients with AMAN, either IgG anti-GM1 and/or anti-GD1a antibodies were positive in 12 (80%) patients. One of the anti-GM1 or GD1b IgG antibody was positive in 2 of the 5 patients with AMSAN. In this study, of the 41 patients positive for antiganglioside antibodies, 25 (61%) patients were positive for GT1b IgG antibodies. The authors have not analysed further to determine any positive correlation between the presence of anti-GT1b IgG antibodies, any specific clinical features and the antecedent infection. The sample is too small to make any meaningful conclusion. About half of the patients with pharyngeal-cervical-brachial variant of GBS carry anti-GT1b antibodies which often cross-react with GQ1b.[9] In the study by Koga et al.,[10] patients with anti-GT1b antibodies that did not cross react with GQ1b, had bulbar palsy, neck weakness, absence of sensory disturbance, and positive C. jejuni serology.

Several studies have suggested pathogenic roles of antiganglioside antibodies in immune-mediated neuropathies.[2],[5],[11] Recent studies have shown that antiganglioside antibody-mediated complement activation plays a key role in the pathogenesis of GBS and related disorders.[11]

In patients with preceding C. Jejuni enteritis, GM1- or GD1a-like lipo-oligosaccharides (LOSs) induce the production of IgG anti-GM1 or anti-GD1a antibodies. These antiganglioside antibodies cross-react with peripheral nerve antigens, causing neuropathy. This molecular mimicry has been well established in AMAN. The possible pathogenesis of AMAN subsequent to C jejuni infection proposed by Yuki[5] suggests that the antibodies bound to GM1 or GD1a at the nodes of Ranvier in peripheral motor nerves induce local complement activation resulting in the formation of membrane attack complex. The autoimmune attack disrupts Nav channels clusters, producing muscle weakness. AMSAN is probably also the result of the the same immune response against the axon rather than the two entities being two separate diseases.[5]

Anti-GQ1b IgG antibodies are pathophysiologically associated with ophthalmoplegia in MFS and GBS, and also with ataxia. GD1b-specific IgG antibodies without cross-reaction to GM1 and other gangliosides induce ataxia and limb weakness in GBS.[11] Yuki[5] proposed the possible mechanism for MFS and related conditions. The IgG anti-GQ1b antibodies bind to the GQ1b that is expressed on oculomotor nerves and muscle spindles, causing the clinical features of MFS or its related conditions.

Antibodies to gangliosides are not found in all the patients with GBS. Antiganglioside antibodies are present in up to 60% of cases of GBS.[11] In the study by Naik et al.,[8] in this issue of Neurology India, of the 204 patients with GBS, antiganglioside antibodies were studied in 73 (35.8%) patients only, and of these, antibodies were present in 41 (56%) patients. The reasons for this observation are not clear. A recent study by Cunningham et al.,[12] showed convincing evidence that anti-ganglioside antibodies are endocytosed at the nerve terminals, removed from the systemic circulation and transported by retrograde axonal transportation to the central nervous system. This may explain to some extent why antiganglioside antibodies may not be present in all the patients with GBS.

References

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