Assessment of anti-ganglioside antibodies in serum of patients exhibiting different types of multiple sclerosis disease in comparison to healthy controls

Gangliosides are glycolipids abundantly expressed on the extracellular layer of several cells in the central nervous system. Gangliosides influence cell-cell interactions, neuronal development, as well as axonal growth and stability and are targets of autoimmunity in several neurological disorders. Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease attributed to the depletion of lipids and myelin components. Anti-ganglioside antibodies (AGA) have been studied in MS, yet their relevance to disease processes remains poorly characterized. Our objective was to compare serum AGA levels between healthy controls (HC) and participants with either a single demyelinating event known as clinically isolated syndrome (CIS), or confirmed MS of relapsing-remitting (RRMS), secondary progressive (SPMS), or primary progressive (PPMS) MS types. Enzyme-linked immunosorbent assays (ELISA) were used to measure levels of antibodies to the gangliosides GA1, GM1, GM2, GD1a, GD1b, and GQ1b. Levels of each AGA measured were not significantly different between HCs and CIS or any MS subgroup. However, they were generally negatively associated with age and there were correlations between several AGAs in MS participants. Predictive modeling demonstrated an inverse relationship between AGAs to GM1 and GD1b, where the likelihood of having MS is increased with higher levels of anti-GM1 and lower levels of anti-GD1b. Higher levels of anti-GD1b and lower levels of anti-GM1 were associated with a greater likelihood of being in the CIS group. Our study showed that patterns and interactions exist between AGA levels amongst different MS groups and that analyzing a single ganglioside is of limited value. The predictive potential of AGA levels to GM1 and GD1b in distinguishing MS type highlight the potential of AGA signatures to aid the discerning disease course and shed light on the underlying pathophysiology of MS.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat