AntiMOG associated encephalomyelitis is an inflammatory demyelinating disease previously considered part of the multiple sclerosis spectrum, and currently considered an independent disease.
Contents
- Conditions related to anti MOG
- Seronegative neuromyelitis optica
- Pediatric demyelination
- Double positive NMO
- Histopathology
- Treatment
- Causes
- History
- Animal models
- References
Antibodies against the Myelin oligodendrocyte glycoprotein have received much of its laboratory attention in studies dealing with multiple sclerosis (MS). Several studies had pointed to a role for antibodies against MOG in the pathogenesis of MS, but most of them were written before the discovery of NMO-IgG and the NMO spectrum of diseases. MOG antibodies are currently considered mostly absent in multiple sclerosis.
Though some patients present brain lesions they do not have the ovoid shape perpendicular to the ventricle typical of MS.
Anti-MOG status is different depending whether it is measured by ELISA or by microarray (CBA). The proper way to identify it is by microarray, reacting patient serum with living cells, and detecting the binding IgG via a fluorescent-labeled secondary antibody.
Conditions related to anti-MOG
The presence of anti-MOG autoantibodies has been associated with the following conditions
Some of them have been studied in detail:
Seronegative neuromyelitis optica
Anti-MOG autoimmunity has been found to be involved in the seronegative NMO and also in optic neuritis and some fulminant forms of ADEM MOG antibodies in NMOSD are variable depending on the seropositivity status
Pediatric demyelination
The anti-MOG spectrum in children is equally variated: Out of a sample of 41 children with MOG-antibodies 29 had clinical NMOSD (17 relapsing), 8 had ADEM (4 relapsing with ADEM-ON), 3 had a single clinical event CIS, and 1 had a relapsing tumefactive disorder. Longitudinal myelitis was evident on MRI in 76[percent]. It has also been noted that percentage of children with anti-mog antibodies respect a demyelinating sample is higher than for adults
Double positive NMO
Some NMO patients present double positive for autoantibodies to AQP4 and MOG. These patients have MS-like brain lesions, multifocal spine lesions and retinal and optic nerves atrophy.
Histopathology
Demyelinating lesions of AntiMOG associated encephalomyelitis resemble MS pattern-II lesions. The demyelinating lesion presents T-cells and macrophages around blood vessels, with preservation of oligodendrocytes and signs of complement system activation.
Treatment
The anti-MOG spectrum has been found to be responsive to steroids, and also to plasmapheresis, as any other pattern-II Inflammatory demyelinating diseases of the central nervous system.
Anti-MOG positive patients should not be treated with interferons. It has been reported to make the disease worse. There are also anecdotal reports against using Fingolimod.
Causes
The causes why anti-MOG antibodies appear in the serum are still not known, but a connection to infectious mononucleosis has been proposed
History
Reports about the involvement of anti-MOG antibodies in MS and other demyelinating diseases were appearing since the late 1980s, but evidence was always weak and inconsistent.
The turning point, was in 2011, when Mader et al. developed a CBA assay using HEK 293 cells and observed that it had a higher specificity to detect anti-MOG in serum. These authors reported that some patients with NMOSD had high titers of anti-MOG antibodies similar to ADEM.
Since that moment, anti-MOG seropositivity has been found consistently in ADEM, NMO, pediatric MS and atypical MS.
Animal models
Animal models of MS, EAE, have shown that “MOG-specific EAE models (of different animal strains) display/mirror human multiple sclerosis" but basically explains the part involved in the optic neuritis These models with anti-MOG antibodies have been investigated extensively and are considered the only antibodies with demyelinating capacity but again, EAE pathology is closer to NMO and ADEM than to the confluent demyelination observed in MS.
Anti-MOG mediated demyelination was shown to behave similar to NMO in animal models, and currently it is considered even a biomarker against the MS diagnosis