Anti-MOG antibodies in Optic neuritis
Optic neuritis is most often a consequence of multiple sclerosis and can lead to partial or complete loss of vision in one or both eyes. Autoimmune mechanisms like producing antibodies against myelin sheath are the causes of this disorder. When idiopathic optic neuritis occurs repeatedly it is considered to be a distinct clinical condition and if accompanied by demyelination it’s believed to be associated with anti-MOG antibodies (
29).
While observing thirty three eyes of 23 patients with optic neuritis and measuring their serum anti-MOG antibodies concentration, 34% of the cases were seropositive (and 26% of cases were seropositive for both MOG and NMO antibodies).This immunoglobulin is considered to be a biomarker to investigate visual prognosis in optic neuritis patients (
30). A study on 37 cases, 18 or under 18 years old with recurrent or single episodes of optic neuritis, suggested that generally these patients had high titer serum anti-MOG antibodies from the subclass of IgG, especially in patients suffering from recurrent episodes of optic neuritis (
31). In a group of pediatrics suffering from recurrent or monophasic ADEM, optic neuritis was diagnosed. Their serum immunoglobulin against MOG protein was measured high titer (
32). It is concluded that anti-MOG antibodies can exert a direct role in optic neuritis pathogenesis. This antibody is significantly associated with bilateral optic neuritis and can play the role of clinical biomarker. Anti-MOG antibody-associated bilateral ON, which is a relapsing disorder, is frequently steroid dependent (
33). And as Tsuburaya stated, recurrent ON patients are candidates for serum anti-MOG antibody analysis (
34).
Anti-MOG antibodies in other disorders
A recent study on 10 arthritis rheumatoid cases resulted in anti-MOG antibody seropositivity in only one patient. It leads to the conclusion that although these antibodies exclusively serve in CNS but we can find them in chronic systemic inflammatory disorders in which CNS is not involved (
35).
A general survey carried out by Mader and his team presented high MOG-IgG serum
concentration in 2/27 of systemic lupus erythematosus (SLE) cases (
36). However exploring serum of 6 systemic lupus erythematosus cases indicated no sign of anti-MOG IgG/IgM (
37).
Treatment
Treatment of MOG spectrum patients is divided in two major parts: treatment of attacks and prevention. The acute phase is generally treated by corticosteroid therapy.
There is no certain agreement about the treatment for MOG spectrum disorder patients however in acute attacks we can use methylprednisolone intravenous (1gr per day, for 3-7 days) for treating acute attacks in patients presented with optic neuritis and transverse myelitis and other symptoms of central nervous system involvement. If the patient showed no response to treatments we can repeat the mentioned dose and plasmapheresis is can be used after intravenous methylprednisolone. Oshiro
et al. reported a 10 year old boy with an NMO spectrum disorder who underwent plasma exchange therapy. Only after anti-MOG antibody serum titer was decreased to the cut-out level did his symptoms obviously stop; however as they suggested further studies are required to establish this method as a therapeutic pathway (
38).
No certain therapy is suggested for prevention yet, however due to recent studies these patients are advised to administrate azathioprine or methotrexate and low dose of prednisolone (for 6-12 months).
A 16 year old girl with optic neuritis accompanied by spinal and cerebral lesions demonstrated anti-MOG antibody seropositivity and fingolimod therapy brought about a relapsing condition. It is suggested
that fingolimod can’t be an effective choice in MOG spectrum disorders (
39).
A general study on patients with ADEM, LETM and NMOSD, all were demonstrating high anti-MOG antibody serum titer, suggested that intravenous immunoglobulin followed by rituximab significantly reduces the relapse rate. While comparing the cases according to their age, it was proved that children with MOG antibody spectrum disorder recovered better after steroid and IVIG therapy (
40).
Relapsing course can be observed in some anti-MOG seropositive patients. These cases fulfill MS diagnosis but they may have a poor response to MS drug treatments like interferon β (
41). An eleven year old girl whose MRI showed transverse myelitis-like lesions, underwent systemic steroid treatment and after initial improvements she lost bowel and bladder control and the lower limb weakness worsened. Vast serum investigations revealed anti-MOG antibody seropositivity; however after frequent courses of plasmapheresis, this condition continued to deteriorate. Finally, extreme immunosuppressive therapy such as cyclophosphamide and rituximab for one year was able to omit further relapses but paraparesis was not eliminated (
42).
Discussion
Myelin Oligodendrocyte Glycoprotein, a CNS exclusive glycoprotein located on the outermost layer of myelin sheath, is produced by oligodendrocytes. This adhesive protein plays an important role in myelin sheath structural integrity and maintenance. Thus any malfunction in MOG protein might result in myelin sheath malformation, which can be seen as signs of demyelinating disorders: For instance immune responses are capable of
endangering MOG molecule entirety. Antibodies against MOG not only bind to the extracellular domain of this protein, but induce natural killer cells to terminate the cells which express MOG (
43).
As mentioned above in a reliable research Egg and his group concluded that Anti-MOG antibodies were present in most cases of Multiple sclerosis, though in contrast with that, with due attention to Jarius
et al. large study’s observing anti-neural antibodies, MOG-IgG might play a noticeable role in a small percentage of cases diagnosed with pattern II MS. Also according to a research performed in 2016 on 104 preselected MS patients, antibodies to MOG were existent in almost 5% of cases. So it seems the elevation of MOG antibodies is not explicit in MS patients. On brain MRI of all seropositive cases lesions were similar to those of typical MS patients. Following them up for more than 9 years to have a longitudinal analysis revealed fluctuations in Anti-MOG antibody serum titer and activity (
9,
12,
44).
While researches done in fields of acute disseminated encephalomyelitis, transverse myelitis, optic neuritis and clinically isolated syndrome were suggesting the important destructive role of anti-MOG antibodies in these disorders, the results were not strongly proved or number of cases were not large enough, therefore further investigations are required to gather a solid opinion on this issue. Nonetheless a research covering the Anti-MOG antibodies in CNS demyelinating diseases, a rare study on this specific subject, reported the following: age is a significant factor in ADEM disease; this means that predominant high titer antibody against MOG was demonstrated in pediatrics. An important finding suggested that recombinant human MOG ELISA couldn’t detect these
antibodies. Other than that these antibodies were rarely frequent in CIS cases’ serum (
13). In contrast with the above study, Brilot
et al. detected Anti-MOG antibodies in 40% of their CIS/ADEM patients by a cell-based bioassay. They also asserted that cases which were seropositive for antibodies were younger, as it was suggested in the previous reference, and that anti-MOG IgG titer was not different between the CIS cases and the ADEM ones (
43).
A recent case report studying on a positive anti-MOG antibody Japanese boy supported the relationship of the former immunoglobulin with Optic Neuritis, although additional research is needed in this field (
7). Anti-MOG antibodies are detected in different kinds of immune-mediated Optic Neuritis; however in NMO related Optic Neuritis they’re not found. By contrast the expression of the mentioned immunoglobulin was significantly higher in MS related Optic Neuritis rather than other NMO spectrum disorders’ group (
45).
To conclude all above it can be stated that Anti-MOG antibodies can be considered as biomarkers for central nervous system autoimmune demyelinating disorders. Detecting these immunoglobulins in patients’ serums can be useful in diagnosis and prognosis pathways. It is possible that anti-MOG antibodies in patients presenting several symptoms such as myelitis, optic neuritis and so on can be sign of a new disease, so we choose MOG spectrum disorder for Anti-MOG antibody seropositive patients presenting mentioned neurological characteristics. Still MOG spectrum disorder is a new term in nervous system demyelinating diseases field.
Conclusion
To conclude all above we can state that for prophylactic treatment of MOG spectrum disorder azathioprine, methotrexate, rituximab and cyclophosphamide are suggested. On the other hand methyl prednisolone and plasmapheresis are suitable for acute phase. Intravenous immunoglobulin can be useful in relapsing forms but it needs more investigations to be proved. According to similar physiopathology of NMOSD and MOG spectrum disorder it is noticeable that fingolimod and interferons may deteriorate the conditions in both of them.
Conflict of Interest
The authors have no conflict of interest.
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