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

RZ Other systems of medicine;Q Science (General)

Rinaldi, Simon ; Willison, Hugh

University:University of Glasgow

Department:Institute of Neuroscience and Psychology

关键词: Guillain-Barré syndrome, ganglioside, ganglioside complexes, neurology, neuroimmunology, lectins, siglecs;   

Others  :  http://theses.gla.ac.uk/3203/1/2011RinaldiPhD.pdf

来源: University of Glasgow

【 摘 要 】

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 suchantibodies are not detected. Recent descriptions of ganglioside complex (GSC) antibodies suggest a potential explanation for this. This study aimed to furtherinvestigate 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.