Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease

Abstract

Myelin oligodendrocyte glycoprotein (MOG) is a candidate target antigen in demyelinating diseases of the central nervous system (CNS). Although MOG is encephalitogenic in different animal models, the relevance of this antigen in human autoimmune diseases of the CNS is still controversial. We investigated the occurrence and biological activity of antibodies to native MOG (nMOG) in 47 children during a first episode of CNS demyelination (acute disseminated encephalomyelitis [ADEM], n = 19 and clinical isolated syndrome [CIS], n = 28) by a cell-based bioassay. High serum immunoglobulin G (IgG) titers to nMOG were detected in 40% of children with CIS/ADEM but 0% of the control children affected by other neurological diseases, healthy children, or adults with inflammatory demyelinating diseases, respectively. By contrast, IgM antibodies to nMOG occurred in only 3 children affected by ADEM. Children with high anti-nMOG IgG titer were significantly younger than those with low IgG titer. Anti-nMOG IgG titers did not differ between the ADEM and CIS group, and did not predict conversion from CIS to MS during a mean 2-year follow-up. However, intrathecal IgG anti-MOG antibody synthesis was only seen in CIS children. IgG antibodies to nMOG not only bound to the extracellular domain of nMOG, but also induced natural killer cell-mediated killing of nMOG-expressing cells in vitro. Overall, these findings suggest nMOG as a major target of the humoral immune response in a subgroup of children affected by inflammatory demyelinating diseases of the CNS. Children may provide valuable insight into the earliest immune mechanisms of CNS demyelination.