Semi-Synthetic Strategies to Obtain Glucosylated MOG to Identify Antibodies as Biomarkers in Multiple Sclerosis Disease

摘要

Several autoimmune diseases have been associated with post-translational modifications (PTMs). In particular, glycosylation is the most important PTM of secreted proteins and plays a crucial role in several immune functions [1]. The role of autoantibodies in autoimmune diseases has been reevaluated and it is accepted that a distinct pattern of Multiple Sclerosis pathology could involve an Ab-mediated demyelination [2]. One of the proposed biomarkers, that may be objectively measured and evaluated as an indicator of normal biological processes, for MS are specific antibodies detectable by immunoassays. Previous studies showed that CSF114(Glc) [3,4], a designed glycopeptide characterized by a β-D-glucopyranosyl moiety on the tip of a I' β-turn, is able to detect and isolate specific autoAbs present in the sera of a significant number of MS patients. Since this synthetic Ag may be considered as a mimetic of aberrantly glucosylated myelin protein(s) triggering autoimmunity in MS, we focused our interest on the role of MOG (Myelin Oligodendrocyte Glycoprotein), a type I integral membrane protein specifically expressed on the outermost lamellae of myelin sheath and considered a putative autoantigen in MS [5]. In order to characterize the molecular mechanisms of the form of MS in which the demyelinization is Ab-mediated, and to design new antigenic probes to detect auto-Ab as biomarkers, the extracellular domain of MOG has been selected as putative autoantigen in these preliminary studies.