Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis. Journal of Neuroinflammation 2011, 8:161 (17 November 2011)
BACKGROUND:Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clinical relevance of these epitopes in MS.
METHODS:Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to MOG isoforms, and quantitative titres correlated with clinical characteristics.
Structure of MOG
RESULTS:In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2 % of samples high-titer anti-MOG antibodies were identified. In patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r=0.574; p=0.025).
CONCLUSIONS:Thus high-titre reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS.
“MOG is one of the few myelin targets that is available to attack by antibodies. In animals immune responses to this protein can drive relapsing neurological attacks and antibodies can induce demyelination. This study suggests that such antibodies present in MS could contribute to problems. However, that these antibodies are not ubiquitous (common to every one) suggests that autoimmunity to this protein cannot fully account for the problems of MS. However it should be said that other studies have reported a higher incidence of anti-myelin antibodies. It is feasible that different people will react to different myelin proteins, as is known and is likely to occur. However, it may suggest such that antibodies can be produced as a consequence of other damaging entities that could trigger this autoimmunity
Do I think that antibodies that react with targets within the CNS are a problem in MS. Well yes I do and I’m pretty sure of that because we can take antibodies for MSers and inject them into animals and see undesirable effects.