Myelin autoimmunity..the delusion complex


Jae-Won Hyun et al. JNNP 2017

Background We evaluated the seroprevalence of myelin oligodendrocyte glycoprotein immunoglobulin G1 (MOG-IgG) and associated clinical features of patients from a large adult-dominant unselected cohort with mainly relapsing central nervous system (CNS) inflammatory diseases. We also investigate the clinical relevance of MOG-IgG through a longitudinal analysis of serological status over a 2-year follow-up period.
Methods Serum samples from 505 patients with CNS inflammatory diseases at the National Cancer Center were analysed using cell-based assays for MOG-IgG and aquaporin-4 immunoglobulin G (AQP4-IgG). MOG-IgG serostatus was longitudinally assessed in seropositive patients with available serum samples and at least 2 years follow-up.
Results Twenty-two of 505 (4.4%) patients with CNS inflammatory diseases were positive for MOG-IgG. Patients with MOG-IgG had neuromyelitis optica spectrum disorder (NMOSD, n=10), idiopathic AQP4-IgG-negative myelitis (n=4), idiopathic AQP4-IgG-negative optic neuritis (n=4), other demyelinating syndromes (n=3) and multiple sclerosis (n=1). No relapses were seen in patients when they became MOG-IgG seronegative, whereas a persistent positive serological status was observed in patients with clinical relapses despite immunotherapy.
Conclusions In a large adult-predominant unselected cohort of mainly relapsing CNS inflammatory diseases, we confirmed that NMOSD phenotype was most commonly observed in patients with MOG-IgG. A longitudinal analysis with 2-year follow-up suggested that persistence of MOG-IgG is associated with relapses.Myelin oligodendrocyte glycoprotein (MOG) is the main antigen to induce EAE, and if you ask an EAEer or c linical immunologists, what is the antigen targeted in MS, they will say myelin basic protein or MOG. But what is the evidence….there is essentially none that is not circumstantial.

MBP is a terrible candidate as it is not CNS restricted and so much work was done with this myelin protein because it was easy to purify and was water soluble. MBP is about 30% of the myelin protein but MOG is less than 1%.   MoG-specific transgenic animals get optic neuritis and spinal cord lesions but do they get MS. 

Well no..animals don’t get MS. But do people with MS have autoimmunity to MOG. The answer is no they don’t and in a group of  people with neuroinflammatory disease few had anti-MOG antibodies and very few of these had MS. Are we deluding ourselves .

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