The application of glycosphingolipid arrays to autoantibody detection in neuroimmunological disorders

• Glycolipids form heteromeric complexes through lateral interaction in lipid membranes.
• A class of antibodies exist that only bind glycolipids when in heteromeric complex.
• Other antibody epitopes may become cryptic when complexed in heteromers.
• Antibodies to glycolipid complexes are associated with peripheral neuropathies.
• Combinatorial glycoarrays can be used to detect anti-complex antibodies.

Humans with autoimmune peripheral neuropathies frequently harbour serum antibodies to single glycosphingolipids, especially gangliosides. Recently it has been appreciated that glycolipid and lipid complexes, formed from two or more individual species, can interact to create molecular shapes capable of being recognised by these autoantibodies whilst not binding to the single individuals. As a result of this, novel autoantibody targets have been identified. 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 lipids of interest. Herein we especially highlight the role of the neutral lipids cholesterol and galactocerebroside in modifying glycosphingolipid orientation that subsequently favours or inhibits autoantibody binding.