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Title: Heterodimeric glycolipid complexes as targets for neuropathy associated pathogenic autoantibodies and other lectins
Author: Rinaldi, Simon
ISNI:       0000 0004 2717 1272
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2012
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RZ Other systems of medicine ; Q Science (General)