Title: Antibodies to MOG in adult and pediatric demyelinating diseases
Description: Although multiple sclerosis (MS) is traditionally thought of as a T cell mediated autoimmune disease, B cells and antibodies can also contribute to the initiation or progression of MS. Antibodies to glial cells may serve as useful biomarkers to help us better understand the mechanisms underlying the spectrum of inflammatory demyelinating diseases and differentiate between clinically similar conditions. Myelin oligodendrocyte glycoprotein (MOG) is an attractive candidate antigen because it is expressed specifically on the surface of the myelin sheath and therefore available for antibody binding in the absence of prior tissue damage. Antibodies to native MOG can contribute to demyelination animal models, while antibodies to denatured protein or peptides are not pathogenic. Many groups have sought to detect MOG-specific autoantibodies in MS patients, but no consensus on the frequency or significance of antibodies to MOG in MS has emerged. We believed this was primarily due to the lack of a good assay for the detection of conformation-sensitive antibodies with low affinity. To address this issue, we developed two methods for the detection of antibodies specific for folded and glycosylated MOG protein in serum or cerebrospinal fluid. The sensitivity of both assays was directly related to the antigen density, and multivalent antigen was necessary for optimal detection of autoantibodies. Using these improved assays, we found that the frequency of antibodies to MOG varied considerably between demyelinating conditions. Anti-MOG was detectable in acute disseminated encephalomyelitis and pediatric-onset MS, but was rarely found in adult-onset MS or other neurological diseases. We believe that antibodies to MOG define a group of patients who share a similar biological mechanism of demyelination.

It may be possible to identify subtypes of demyelinating diseases based on the autoimmune processes involved rather than relying on clinical features alone.