The application of glycosphingolipid arrays to autoantibody detection in neuroimmunological disorders

Galban Horcajo, Francesc (2014) The application of glycosphingolipid arrays to autoantibody detection in neuroimmunological disorders. PhD thesis, University of Glasgow.

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Abstract

Serum autoantibodies directed towards a wide range of single glycosphingolipids, especially gangliosides, in humans with autoimmune peripheral neuropathies have been extensively investigated since the 1980s and these are widely measured both in clinical practice and research. It has been recently appreciated that glycosphingolipid and lipid complexes, formed from 2 or more individual components, can interact to create molecular shapes capable of being recognised by autoantibodies that do not bind the individual components. Conversely, 2 glycosphingolipids may interact to form a heteromeric complex that inhibits binding of an antibody known to bind one of the partners. As a result of this, previously undiscovered autoantibodies have been identified, providing substantial new insights into disease pathogenesis and diagnostic testing. In particular, this newly-termed ‘combinatorial glycomic’ approach has provided the impetus to redesigning the assay methodologies traditionally used in the neuropathy-associated autoantibody field. Combinatorial glycoarrays can be readily constructed in house using any lipids and glycosphingolipids of interest, and as a result many new antibody specificities to gangliosides and other glycosphingolipid complexes are being discovered in neuropathy subjects. Herein we also highlight the role of the neutral lipids cholesterol and galactocerebroside in modifying glycosphingolipid orientation as two critical components of the molecular topography of target membranes in nerves that might favour or inhibit autoantibody binding.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Two of the chapters contained within the thesis are part of scientific published material.
Keywords: glycosphingolipid,Combinatorial glycoarrays,autoantibody binding
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Immunology
Funder's Name: UNSPECIFIED
Supervisor's Name: Willison, Professor Hugh
Date of Award: 2014
Depositing User: Mr. Francesc Galban Horcajo
Unique ID: glathesis:2014-5030
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Apr 2014 07:24
Last Modified: 11 Apr 2014 07:26
URI: http://theses.gla.ac.uk/id/eprint/5030

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