Insights into glycosylation-driven immune recognition in autoimmune demyelinating disorder of the CNS by using synthetic glycopeptides as antigenic probes
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOG-AD) is an autoimmune demyelinating disorder of the central nervous system characterized by antibodies against myelin oligodendrocyte glycoprotein (MOG), now recognized as the defining biomarker of the disease. Diagnosis currently relies on cell-based assays (CBAs), which, despite being the gold standard, remain technically demanding and limited to specialized centers. Previously, we showed that N-glucosylated myelin-derived peptides are selectively recognized by autoantibodies in multiple sclerosis (MS) and cross-react with HMW1, a hyperglucosylated adhesin from nontypeable Haemophilus influenzae (NTHi), supporting a role for aberrant glycosylation and molecular mimicry in autoimmune demyelination. Since MOG is the specific antigenic target in MOG-AD, we investigated whether similar glycosylation-dependent immune recognition occurs in this disease. A panel of MOG(25-55)-derived peptides, encompassing the immunodominant region and the native glycosylation site (Asn31), was synthesized in different site-specifically N-glucosylated analogues at Asn31, Asn53, or both. Their antigenicity was evaluated by ELISA using sera from MOG-AD, MS, and NMOSD patients, alongside HMW1 reactivity. Preliminary results show preferential IgG recognition of glucosylated MOG peptides, correlating with the degree of glucosylation and being stronger near disease relapse. These findings provide new insights into glycosylation-dependent immune recognition in MOG-AD and could be the basis for the development of a more accessible and higher-throughput assay. Ongoing work focuses on multivalent glucosylated probes and full-length N-glucosylated hMOG.
Last update
22.07.2026