Biomolecular Chemistry

New project: Are glycans crucial determinants of autoantibody reactivity in multiple sclerosis?

The Stichting MS Research has awarded a project aimed at elucidating the role of sugars in the autoimmune response in multiple sclerosis (MS). Autoimmune reactions against central nervous system (CNS) proteins likely contribute to MS onset and progression. Autoantibodies against CNS proteins are present in individuals with MS and constitute promising minimally invasive biomarkers for disease detection and monitoring. However, no robust autoantibody-test exists for MS and their development is limited by the lack of specific autoantibody targets. Post-translational modifications of proteins can generate immunogenic sequences recognized by autoantibodies. The most diverse protein modification is glycosylation, the addition of structurally diverse chains of sugar molecules (glycans). Glycans direct protein conformation, sterically hinder or enable access to peptide epitopes, and can be recognized directly as antigens. In this pilot project the role of glycosylation in the autoantibody response in MS will be unexplored. The results will identify specific glycosylation-dependent interactions between MS autoantibodies and CNS proteins. This will provide evidence that (altered) glycosylation plays an important role in autoantibody formation in MS and will not only form the basis for studying the contribution of glycosylation in the development of MS, but will also facilitate the development of tests for MS diagnostics and surveillance.

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