What is Myelin Oligodendrocyte Glycoprotein (MOG)?
MOG is a membrane-bound glycoprotein located exclusively on the outermost surface of myelin sheaths and oligodendrocyte cell membranes in the central nervous system, serving as the target antigen in MOG antibody-associated disease (MOGAD), a distinct autoimmune inflammatory demyelinating disorder separate from multiple sclerosis and neuromyelitis optica spectrum disorders. 1, 2
Molecular Structure and Location
- MOG belongs to the immunoglobulin superfamily and contains an extracellular N-terminal domain with conserved immunoglobulin variable region folds 3
- The protein is expressed primarily in the brain, spinal cord, and optic nerves, appearing solely on the outer membrane of myelin sheaths 1, 4
- Its unique outmost location makes it an accessible target for autoimmune antibodies and cell-mediated immune responses in demyelinating processes 4
Biological Function
- MOG likely functions as a cell surface receptor or cell adhesion molecule, though its exact physiological role remains incompletely understood 4, 5
- It serves as an important marker of oligodendrocyte maturation, appearing 1-2 days later than other oligodendrocyte markers like galactocerebroside and myelin basic protein during development 6
- The protein's late postnatal developmental expression makes it a key indicator of oligodendrocyte maturation 7
Clinical Significance in Disease
- Pathogenic antibodies against full-length MOG protein (MOG-IgG) cause MOGAD through direct immunological mechanisms, with intralesional complement and IgG deposits demonstrating primary demyelination distinct from MS pathology 1
- MOGAD presents most commonly with optic neuritis (most frequent in adults), transverse myelitis with longitudinally extensive lesions affecting ≥3 vertebral segments, or acute disseminated encephalomyelitis (most common in children) 2
- The disease is immunopathogenetically distinct from both multiple sclerosis and aquaporin-4-positive neuromyelitis optica spectrum disorders, with near-complete absence of AQP4 antibodies 1
Disease Course Patterns
- Adults with MOGAD experience a relapsing course in at least 80% of cases, while children more commonly have monophasic disease, particularly with ADEM presentations 1
- A significant proportion (33%) of adult patients meet McDonald's criteria for MS at some point during their disease course, leading to frequent historical misdiagnosis 2
Critical Diagnostic Considerations
- Detection of MOG antibodies requires cell-based assays using full-length human MOG as the target antigen—peptides or denatured protein are inadequate 2
- Serum is the specimen of choice for testing, not CSF, because MOG-IgG is produced extrathecally with higher serum titers than CSF 2
- MOG-IgG titers are disease-activity dependent and should be retested during acute attacks, treatment-free intervals, or 1-3 months after plasma exchange/IVIG if initially negative but clinical suspicion remains high 8
Treatment Implications
- Misclassification as MS has critical therapeutic consequences—beta-interferons, natalizumab, and fingolimod can exacerbate MOGAD due to differences in immunopathogenesis 8, 2
- Patients show particular responsiveness to antibody-depleting treatments (plasma exchange, immunoadsorption) and B cell-targeted therapies like rituximab 2
- High-dose intravenous methylprednisolone is first-line for acute attacks, with mandatory slow steroid taper due to high risk of flare-ups after rapid cessation 8