Oligodendrocyte Glycoprotein Antibody Research Articles

Seroprevalence of anti-myelin oligodendrocyte glycoprotein antibodies in adults with myelitis.

Although myelitis is the second most common presentation in adults with myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD), studies on MOG‐IgG seroprevalence in patients with myelitis episodes are sparse. Herein, we investigated MOG‐IgG seroprevalence in Korean adults who exhibited myelitis since 2017. Among 151 adults with acute myelitis, 11 (7.3%) tested positive for MOG‐IgG by the initial screening and 10 (6.6%) patients were finally diagnosed with MOGAD during the study period. This study is the first to provide data on MOG‐IgG seroprevalence in adults with myelitis and supports the clinical utility and importance of MOG‐IgG testing in myelitis episodes.

Is there a correlation between MOG-associated disorder and SARS-CoV-2 infection?

Background and purposeAnti‐myelin oligodendrocyte glycoprotein antibodies (MOG‐Abs) distinguish a group of inflammatory disorders which can be preceded by specific or non‐specific infections. A few single cases have been reported in association with SARS‐CoV‐2 infection, but a specific study on the correlation between COVID‐19 and myelin oligodendrocyte glycoprotein (MOG)‐associated disorder (MOGAD) has not yet been performed. The aim of this study was to determine the impact of the pandemic on this condition.MethodsWe analysed SARS‐CoV‐2 serology in patients newly diagnosed with MOGAD (1 August 2020 to 31 May 2021). MOG‐Ab‐seronegative age‐ and time‐matched subjects were used as controls. SARS‐CoV‐2 immunoglobulin G (IgG) levels were analysed using an anti‐SARS‐CoV‐2 US Food and Drug Administration‐approved ELISA assay and confirmed with a trimeric anti‐SARS‐CoV‐2 S1/S2 IgG immunochemiluminescent test, concomitantly assaying the anti‐receptor binding domain (RBD) of spike protein IgG and anti‐RBD total Ig. We actually compared the number of cases referred in each of the last 3 years.ResultsPresence of SARS‐CoV‐2 IgG antibodies was more common (12/30, 40%) in MOGAD patients than in controls (6/30, 20%), although the difference was not significant (p = 0.16; odds ratio 2.67, 95% confidence interval 0.85–9.17). The most common clinical presentations of MOGAD SARS‐CoV‐2‐seropositive patients included optic neuritis (n = 6) and myelitis (n = 3). The number of diagnosed cases increased over the last 3 years, in particular, when including cases referred to us before the COVID‐19 pandemic, in the initial phase of the first wave and in the late phase of the second wave (n = 9, rate 10.6% in 2019; n = 13, rate 12.3% in 2020; n = 15, rate 14.7% in 2021).ConclusionOur findings provide preliminary data on SARS‐CoV‐2 as a potential trigger of MOGAD.

Paediatric Acquired Demyelinating Syndromes

Paediatric acquired demyelinating syndromes (ADS) are characterised by neurological deficits persisting for at least 24 hours, involving the optic nerve, spinal cord or brain with a clinical spectrum of diagnoses including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and MOG-Ab associated disease (MOGAD). Important strides have been made in delineating MS from other ADS subtypes over the past decade, including the discovery of serum aquaporin-4 (AQP4) and Myelin oligodendrocyte glycoprotein (MOG) antibodies (Ab). Both genetic (e.g. human leukocyte antigen, HLA-DRB1*1501 allele) and environmental risk factors (e.g. low serum vitamin D levels and prior exposure to Epstein–Barr virus) may contribute to risk of MS in children. Some of these risk factors not only confer increased susceptibility to MS but may also affect the disease course. Paediatric AQP4-Ab NMOSD is a rare disease worldwide but variations in incidence/prevalence have been described among different geographic regions and ethnicities. One-third of children who present with an ADS have MOG-Ab, and approximately half of patients with MOG-Ab have a relapsing disease course. It seems there is no racial or gender predominance in MOGAD, which is in contrast to the female and non-white predominance seen in both MS and NMOSD.‎ In this review, we examine the current literature regarding the epidemiology and demographics of these different ADS entities with a particular focus on the genetic and environmental risk factors for MS in children. While insights into disease pathophysiology in paediatric ADS have led recent therapeutic advances, well designed, collaborative large scale epidemiological studies are likely to provide the critical next step to a personalised approach to these conditions.

Epilepsy in patients with MOG antibody disease

Introduction. MOG (anti-myelin oligodendrocyte glycoprotein) antibody disease is a group of demyelinating disorders of the central nervous system, in which antibodies attack the glycoproteins on the oligodendrocyte myelin membrane. The aim of the study was to evaluate the course of the disease in patients with MOG antibody disease with epilepsy.
 Materials and methods. We examined 11 patients (5 men and 6 women) with MOG antibody disease aged from 2 months to 46 years. Three case studies were described when patients with MOG antibody disease had epileptic seizures.
 Results and discussion. Epileptic seizures preceded the diagnosis of MOG antibody disease in the first patient. The disease presented as right-sided optic neuritis in the second patient. Seven years later, an epileptic seizure occurred after childbirth, when the BBB could have become permeable to circulating MOG antibodies. The disease presented with headache in the third patient. Right-sided optic neuritis and ataxia developed after an acute viral respiratory infection. Myelitis was diagnosed, and an epileptic seizure occurred one year later. The patient had a combination of CADASIL syndrome with MOG antibody disease.
 Conclusion. Epileptic seizures are common in patients with MOG antibody disease. In addition to antiepileptic therapy, treatment of MOG antibody disease is crucial. This leads to good seizure control and a favourable prognosis.

Anti-Myelin Oligodendrocyte Glycoprotein Encephalomyelitis and Extensive Longitudinal Transverse Myelitis Associated with Compound Heterozygous NLRP3 Missense Mutations in a Young Child

AbstractAcute disseminated encephalomyelitis in association with extensive longitudinal transverse myelitis is reported in a young child with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody with heterozygous NLRP3 missense mutations; p.(Arg488Lys) and p.(Ser159Ile). This case may well present an exceptional coincidence, but may describe a yet unrecognized feature of the spectrum of childhood onset cryopyrinopathies that contribute to the understanding of the genetic basis for anti-MOG antibody positive encephalomyelitis. Based on this observation, a larger scale study investigating the role of NLRP3 and other inflammasomes in this entity would provide important pathophysiological insights and potentially novel avenues for treatment.

Anti-MOG Antibody Syndrome and Cerebral Sinovenous Thrombosis: A Cause–Effect Hypothesis

AbstractCerebral venous thrombosis is an uncommon event of stroke in childhood. Its origin is multifactorial and often it manifests with nonspecific symptoms that may overlap with underlying predisposing factors. Anti–myelin oligodendrocyte glycoprotein (MOG) antibody syndrome is a group of recently recognized acquired demyelinating diseases that occur more commonly in children, usually, with a favorable outcome. The association between cerebral venous thrombosis and demyelinating syndrome has been reported but their clinical relationship is matter of debate and various hypotheses have been advanced including intravenous (IV) steroid therapy and/or the consequence of a shared inflammatory-thrombotic process. Herein, we report the case of a child with anti-MOG antibody syndromes who developed a thrombosis of the superior sagittal sinus and of the right Trolard's vein.

Perivenous demyelination: Association with anti‐myelin oligodendrocyte glycoprotein antibody

AbstractBy the discovery of an antibody to aquaporin 4 (AQP4), the clinical and radiological findings of neuromyelitis optica (NMO) such as diffuse cerebral or longitudinally extended spinal cord lesions had been clarified as distinct features from multiple sclerosis (MS). Pathological studies in NMO demonstrated loss of immunoreactivity to AQP4 and glial fibrillary acidic protein but a relative preservation of myelin basic protein, especially at the lesions with perivascular deposition of immunoglobulins and complements, suggesting autoimmune disease against astrocytes. In recent years, the antibody against myelin oligodendrocyte glycoprotein (MOG) has been studied for its association with acute demyelinating diseases such as acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM), optic neuritis, AQP4 antibody–negative NMOSD, and brainstem or cerebral cortical encephalomyelitis. We could identify the dominance of perivenous inflammatory demyelination like ADEM in our biopsied case series with MOG antibody. In recent brain‐biopsied cases with MOG antibody, the deposition of humoral immunity, perivascular inflammation, and perivenous demyelination were observed especially in atypical cases including cortical encephalitis or disseminated encephalitis. In this review, we focus on MOG antibody–related diseases, which we considered it as a differentiated disease from MS by means of the disease‐specific autoantibody and the distinct pathophysiology.

MOG Antibody–Associated Encephalitis in Children

To characterize myelin oligodendrocyte glycoprotein (MOG) antibody–associated demyelinating and encephalic pediatric syndromes, investigators in Spain

Comparison of MRI features of first-episode optic neuritis with positive AQP4 and MOG antibodies

Objective To explore the MRI features of acute optic neuritis with positive aquaporin-4 (AQP4) antibodies and myelin oligodendrocyte glycoprotein (MOG) antibodies during the first attack. Methods Eighty five patients (105 affected nerves) with first-episode AQP4-seropositive optic neuritis (AQP4-ON; n=58; 64 affected nerves) and MOG-seropositive optic neuritis (MOG-ON; n=27; 41 affected nerves) diagnosed by our hospital Neuro-ophthalmology Department between April 2014 and December 2017 were retrospectively analyzed. Double seronegative patients or double seropositive patients were not included. All patients underwent orbital conventional MRI; 29 patients also underwent RESOLVE-DWI and 55 underwent brain T2 fluid-attenuated inversion recovery (T2FLAIR).Theclinical features (age, gender, disease duration) and MRI features (T2WI, bilateral involvement, the degree and extent of enhancement, the extent of involvement, the affected segment and ADC values of nerve; demyelinating lesions of brain) were analyzed by 2 doctors. The qualitative parameters were compared with χ2 test or Fisher exact test and the quantitative parameters were compared with two independent sample t test (normal distribution) or the Mann-Whitney U test (skewed distribution). The Kappa test was used to test the consistency of the qualitative characteristics of the images evaluated by the 2 doctors. The interclass correlation coefficient (ICC) was used to test the consistency of the ADC obtained by the 2 doctors. Results There were no significant differences in the distributions of age and disease duration between 2 groups (t=1.911, Z=-1.054, P>0.05). AQP4-ON had a higher female proportion (χ2=13.911, P 0.05). There was a higher probability of optic nerve swelling, long segmental lesions and optic nerve head involvement in MOG-ON(χ2=16.845, 13.525, 13.264, P<0.05). Moreover, the rate of obvious enhancement and the involvement of optic chiasm was higher in AQP4-ON(χ2=7.152, 5.088, P<0.05). RESOLVE-DWI showed the ADC values of the AQP4-ON were significantly lower than those of MOG-ON (t=-3.300, P<0.05). The qualitative features of image evaluated by the 2 doctors were consistent well (Kappa=0.712-0.932, P<0.001) .The ADC values obtained by the 2 doctors were consistent well (ICC=0.942, P<0.001). Conclusions For the first-episode acute optic neuritis, AQP4-ON hasobvious female predilection and the trend of unilateral involvement and obvious enhancement, while MOG-ON isoften involved bilaterally with longitudinally extensive lesions.The ADC values of the AQP4-ON are significantly lower than those of MOG-ON and AQP4-ON are more vulnerable to involve the optic chiasm. Conventional MRI and RESOLVE-DWI are helpful for differentiating AQP4-ON from MOG-ON during the early stage of the disease course. Key words: Optic neuritis; Magnetic resonance imaging; Antibodies; Aquaporin 4; Myelin oligodendrocyte glycoprotein

Correlation of serum aquaporin 4 antibodies and condition and visual prognosis in patients with severe neuromyelitis optica spectral disorders

Objective To observe the correlation of serum aquaporin 4 (AQP4) antibodies and condition and visual prognosis in patients with severe neuromyelitis optica spectral disorders (NMOSD). Methods Fifty NMOSD patients with visual acuity of 20/200 or worse in at least one eye were enrolled in this retrospective analysis. There were 12 males and 38 females. The age ranged from 17 to 65 years, with the mean of (39.86±2.02) years. The patients were divided into two groups according to the serum AQP4-IgG status. The ophthalmologic examination, serum anti-nuclear antibodies (ANA), myelin oligodendrocyte glycoprotein (MOG) antibody detection and vision prognosis were compared and analyzed. Glucocorticoid therapy was delivered to 46 patients who were within 1 month of onset. The visual acuity of the patients after treatment was divided into complete recovery, partial recovery, stabilization and reduction, and the visual acuity of the two groups were analyzed. Results Among 50 patients, there were 30 (60%) seropositive patients (positive group), 20 (40%) seronegative patients (negative group). The positive group had significantly higher ratio of female to male (P=0.004), and more binocular optic neuritis (ON) (P=0.010) compared with the negative group. More recurrence ON were also found in the positive group, but without statistic difference between two groups (P=0.167). There was no difference of age, course, and vision damage degrees and abnormal orbital MRI scanning between two groups (P>0.05). Among 24 patients who underwent serum ANA detection in the positive group, 8 patients were positive. All of 18 patients who underwent serum ANA detection in the negative group were negative. The difference of the ratio of serum ANA positive patients between two groups was significant (P=0.030). Serum MOG antibody detection in the positive group was negative (0/10). Sixteen patients who underwent MOG antibody detection in negative group, 4 patients were positive. After treatment, there were 23.3%, 23.3%, 53.3% patients with vision of complete recovery, partial recovery and reduction in the positive group; 25.0%, 30.0%, 25.0% patients with vision of complete recovery, partial recovery and reduction in the negative group, respectively. There was no difference in proportion of vision with complete recovery and partial recovery between two groups (P=0.163, 0.607), but significant difference was observed in proportion of vision with stabilization and reduction between two groups (P=0.021, 0.048). Conclusions The positive serum AQP4 antibody is common in patients with severe NMOSD. The patients with AQP4 antibody in the serum are more likely combined with immunological serological markers and poor vision prognosis. Key words: Neuromyelitis optica; Visually impaired persons; Aquaporin 4

Diagnostic Challenges in Pediatric Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

AbstractThis review highlights the most common presentations of demyelination of the central nervous system (CNS, termed acquired demyelinating syndrome) in children, the difficulty in determining whether the first episode represents a monophasic/transient illness or relapsing disease, and the potential underlying etiologies that must be considered, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and disorders associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) antibodies. The initial clinical and magnetic resonance imaging (MRI) features, as well as those observed over time, are highlighted, emphasizing the distinct and overlapping features of each of these disorders.

Case of steroid‐responsive unilateral encephalitis with anti‐myelin oligodendrocyte glycoprotein antibodies

Case of steroid‐responsive unilateral encephalitis with anti‐myelin oligodendrocyte glycoprotein antibodies

Boundary between multiple sclerosis and neuromyelitis optica

AbstractMultiple sclerosis and neuromyelitis optica spectrum disorders are often indistinguishable by their clinical features. Recently, anti‐myelin oligodendrocyte glycoprotein antibody was found in the serum of neuromyelitis optica spectrum disorders patients without anti‐aquaporin‐4 antibody. This finding suggests a new category of central nervous system demyelinating diseases. However, even with the information provided by these serum antibody results, the diagnoses of some patients remain problematic. In the present article, a case that appeared to be at the boundary between multiple sclerosis and neuromyelitis optica are presented. The patient was a 41‐year‐old woman who developed relapsing myelitis. Spinal cord magnetic resonance imaging showed a relatively long lesion. She had not developed brain lesions on routine magnetic resonance imaging for more than 5 years. She was negative for anti‐aquaporin‐4 antibody, and oral prednisolone could not prevent her relapses. However after fingolimod administration, she became stable and Expanded Disability Status Scale gradually improved.

Autoantibodies in patients with neuromyelitis optica

Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system (CNS) which primarily involves the optic nerve and spinal cord. Aquaporin 4 (AQP4) is the main objective antigen, and its specific antibody was NMO-IgG. It was found in clinic that most of NMO-IgG-positive patients were female, whose clinical symptoms were more severe, bilateral optic neuritis (BON) or optic neuritis (ON) and myelitis were more likely to appear at the same time, and involved spinal segments were longer. Recent studies discovered that anti-aquaporin 1 (AQP1) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies existed in the serum of patients with NMO-IgG-negative. It was discovered that low proportions of women, more cases of long-segment spinal cord lesion, and rare cases of ON appeared in anti-AQP1 antibody-positive patients. Most of anti-MOG antibody-positive patients were male. ON was common, especially bilateral optic nerves involved at the same time, and thoracolumbar involvement was common. DOI: 10.3969/j.issn.1672-6731.2016.10.004

Anti‐myelin oligodendrocyte glycoprotein antibody in demyelinating diseases

AbstractAnti‐myelin oligodendrocyte glycoprotein (MOG) antibody, which is specifically detected using a cell‐based assay (CBA), has been identified in various demyelinating diseases, including neuromyelitis optica spectrum disorders (NMOSD), acute idiopathic optic neuritis (ON), and pediatric multiphasic disseminated encephalomyelitis. Although its pathogenic role has not been established, antibody seropositive cases appear to share several characteristic features, such as a preferable response to steroid therapy and a good prognosis. Antibody detection at the onset of a demyelinating disease is important to predict the prognosis. Further analysis of the clinical features and investigation of the pathogenic roles of the antibody are required to establish the disease spectrum associated with the antibody. Although the associated diseases appear to have a relatively good prognosis, treatment recommendations are offered for patients with severe symptoms or frequent relapses.

OP65 – 3006: Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies

Myelin oligodendrocyte glycoprotein (MOG) antibodies have been recently reported in recurrent optic neuritis, aquaporin-4 antibody negative neuromyelitis optica and acute disseminating encephalomyelitis. Objective To describe the MOG antibody status, clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis (MDEM). Methods Clinical course, cerebrospinal fluid-, MRI studies and outcome of children with MDEM and serum MOG antibody status referred from different hospitals were reviewed. Results 9 children with two or more episodes (range 2 to 6) fulfilling the IPMSSG criteria of ADEM and serum MOG antibodies were identified. Median age at initial presentation was 4 years (range: 2 to 8 years). Median CSF cell count was 9/μl (range: 0 to 85/μl). OCBs tested in 7/9 children were present only in one child. Serum samples were available from all children from at least one acute episode. Median serum MOG antibody level was 1:1280 (range from 1:160 to 1:10240). One or more follow-up samples were available from 5 children showing persisting MOG antibodies overtime in all samples. Clinical outcome did range from normal (2/9), mild/moderate impairment with neuropsychological or motor deficits (3/9) to significant neurological sequelae (2/9). MR-imaging showed in general multiple hazy and large lesions which resolved or diminished in size before the next episode of ADEM occurred. In children with a moderate or severe neurological sequelae follow-up MRIs revealed large confluent lesions or generalized atrophy. Conclusion A subgroup of children with MDEM has high and persisting MOG antibodies extending the spectrum of MOG antibody associated diseases.

Persistent Presence of the Anti-Myelin Oligodendrocyte Glycoprotein Autoantibody in a Pediatric Case of Acute Disseminated Encephalomyelitis Followed by Optic Neuritis

We report the case of a 5-year-old Japanese girl who initially had acute disseminated encephalomyelitis (ADEM) and was positive for the myelin oligodendrocyte glycoprotein (MOG) antibodies and developed unilateral optic neuritis (ON) 71 days after ADEM onset. The patient's serum was positive for the anti-MOG antibodies from the onset of ADEM to the development of ON. This phenotype has been reported in only two previous articles, and the specific mechanism of action of the anti-MOG antibodies is not yet understood. Our case suggests that the anti-MOG antibody can be associated with the pathogenesis of ADEM followed by ON. Thus, patients with ADEM who test positive for the anti-MOG antibody may be at risk of developing subsequent ON.

Pertussis vaccine-induced experimental autoimmune encephalomyelitis in mice

Abstract