Brennan, Kathryn M.
The development and use of combinatorial glycoarrays to investigate anti-glycolipid antibodies in neurological disease.
PhD thesis, University of Glasgow.
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The observation that cis interactions of neighbouring gangliosides could influence the binding capabilities of anti-glycolipid antibodies has revolutionised the glycolipid world. The realisation of the importance of these interactions has necessitated a novel platform to be developed to assay antibody to a high number of potential glycolipid antigens and their combinations (complexes). I have developed a combinatorial glycoarray technique to assay serum anti-glycolipid and anti-glycolipid complex antibodies and investigated their frequency in two populations of patients with peripheral neuropathy, Guillain Barré Syndrome and Chronic Inflammatory Demyelinating Polyneuropathy. I have compared this technique to the standardized well established technique of assaying glycolipids antibodies, namely enzyme-linked immnosorbent assay (ELISA).
In addition I have employed this platform to illustrate the presence of anti-lipid antibodies within the cerebrospinal fluid (CSF) of Multiple Sclerosis (MS) patients. Furthermore though collaboration with other investigators I have demonstrated that oligoclonal immunoglobulin bands (OCB) present in the CSF of MS patients are lipid reactive. This is the first time since their original description over 50 years ago that the specificity of MS derived OCB has been described. Whilst the pathological significance of these lipid reactive antibodies remains uncertain their description provides new avenues for future research.
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