Projects / Autoimmune mediate diseases / Multiple Sclerosis

Towards semi-synthetic N glucosylated MOG to identify aberrantly modified native protein autoantigens in multiple sclerosis

Profiles

In collaboration with:

Laboratory of BioMolecules, UPMC- CNRS-ENS, Paris, France

F. Burlina, Solange Lavielle

Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system characterized by demyelination. This disease is a major cause of disability in adult Caucasians and affects about 1 per million people in the world. Its etiology and pathogenesis have not yet been completely characterized. As a distinct pattern of MS could involve an antibody-mediated demyelination, identification of autoantibodies as specific biomarkers is a relevant target. Even if interesting data focused on the diagnostic and prognostic role of the detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) in adults’ serum, its value remains dubious due to many other contrasting results. Our research group identified CSF114(Glc), an N-glucosylated peptide, able to detect disease-specific autoantibodies in the sera of a statistically significant number of MS patients. Since this synthetic antigen may be considered as a mimic of aberrant post-translational modification (i.e. N?glucosylation) of myelin protein(s) triggering autoimmunity in MS, our goal is to obtain the extracellular domain of MOG properly glucosylated thanks to a simplified native chemical ligation approach. For this purpose, the N-glucosylation will be introduced in a synthetic peptide fragment following the building-block approach by SPPS. The other protein fragment bearing an N-terminal cysteine will be expressed in E. coli after introduction of a selective point mutation into MOG. Finally, our aim is to test the semi-synthetic protein by SP-ELISA to study the ability to detect autoantibodies in MS patients’ sera and to find a potential cross-reactivity with CSF114(Glc).