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Heterodimeric glycolipid complexes as targets for neuropathy associated pathogenic autoantibodies and other lectins

Rinaldi, Simon (2012) Heterodimeric glycolipid complexes as targets for neuropathy associated pathogenic autoantibodies and other lectins. PhD thesis, University of Glasgow.

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Abstract

There is plentiful evidence that the pathology of Guillain Barré syndrome (GBS) is driven by autoantibodies generated following infection. A number of inconsistencies with this theory remain, and in many clinical cases such antibodies are not detected. Recent descriptions of ganglioside complex (GSC) antibodies suggest a potential explanation for this. This study aimed to further investigate GSCs and associated antibodies with a particular focus on GBS. GSCs were found to modulate the binding of other lectins such as bacterial toxins, immunomodulatory receptors, and monoclonal antibodies. The development of a semi-automated array system allowed screening of a large cohort of GBS sera against multiple complexes, revealing a greater antibody detection rate (particularly in demyelinating forms) than had previously been achieved. Binding that was both enhanced and attenuated by complexes was seen, and this varied between disease and control sera. Immunisation experiments provided insights into the generation of the GSC immune response. A transgenic mouse model of GBS was also developed, demonstrating that local axonal expression of gangliosides does not induce systemic tolerance. The work described in this thesis has thus significantly advanced knowledge in the field of glycolipid complexes, particularly with respect to anti-glycolipid complex antibodies and their association with inflammatory neuropathies such as Guillain-Barré syndrome.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Guillain-Barré syndrome, ganglioside, ganglioside complexes, neurology, neuroimmunology, lectins, siglecs
Subjects: R Medicine > RZ Other systems of medicine
Q Science > Q Science (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Supervisor's Name: Willison, Prof. Hugh
Date of Award: 2012
Depositing User: Dr Simon Rinaldi
Unique ID: glathesis:2012-3203
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 28 Feb 2012
Last Modified: 10 Dec 2012 14:05
URI: http://theses.gla.ac.uk/id/eprint/3203

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