Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton

Dale, Russell C.; Tantsis, Esther; Merheb, Vera; Kumaran, Raani; Sinmaz, Nese; Pathmanandavel, Karrnan; Ramanathan, Sudarshini; Booth, David R.; Wienholt, Louise; Prelog, Kristina; Clark, Damien R.; Guillemin, Gilles J.; Lim, Chai K.; Mathey, Emily K.; Brilot, Fabienne

doi:10.1212/nxi.0000000000000012

Cited by 154 publications

(176 citation statements)

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“…Anti-MOG antibodies occur more frequently in children than in adults and have been described (using different assays which, as noted above, may affect findings) in pediatric patients with a variety of autoimmune demyelinating disease phenotypes, including those of ADEM, MS, 32,[35][36][37] relapsing ADEM, relapsing ON, 38,39 relapsing ADEM-ON, 40 and relapsing ON-longitudinally extensive TM (NMO-like). 36,37 The normal function of MOG, which resides at the cell surface of oligodendrocytes, is not well understood.…”

Section: Cns-directed Antibodies In Pediatricmentioning

confidence: 99%

“…36,37 The normal function of MOG, which resides at the cell surface of oligodendrocytes, is not well understood. There is a dominant epitope involved in MOG IgG binding on the extracellular domain 13 and evidence of MOG IgG pathogenicity including alteration of oligodendrocyte cytoskeleton, 38 as well as implication in both complement-dependent and cell-based cytotoxicity. 35,41,42 A recent pathology report demonstrated antibody and complement deposition in an adult case of anti-MOG antibody-associated demyelination.…”

Section: Cns-directed Antibodies In Pediatricmentioning

confidence: 99%

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Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

et al. 2016

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Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric-and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing. CSF analysis in pediatric-onset MS points to chronic CNS inflammation, supported by observations from limited pathologic material available for study. Emerging results implicate abnormalities in both effector and regulatory T cell subsets, and potentially immune senescence, in children with MS. Although CNS-directed antibodies (including antibodies recognizing myelin antigens; Kir4.1) can be documented in pediatric-onset MS, their pathophysiologic significance (as in adults) remains unclear. This is in contrast to the presence of serum and/or CSF antibodies recognizing aquaporin-4, which, when measured using validated cell-based assays, supports the diagnosis of a neuromyelitis optica spectrum disorder, distinct from MS. Presence of anti-myelin oligodendrocyte glycoprotein antibodies documented with similar cell-based assays may also be associated with pathophysiologically distinct disease phenotypes in children. The substantial impact of pediatriconset MS on normal brain development and function underscores the importance of elucidating both the immunobiology and neurobiology of disease. Ongoing efforts are aimed at developing and validating biological measures that define pathophysiologically distinct monophasic and chronic forms of pediatric CNS demyelination. Neurology ® 2016;87 (Suppl 2):S12-S19 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; AQP4 5 aquaporin-4; BBB 5 blood-brain barrier; CBA 5 cell-based assay; EDSS 5 Expanded Disability Status Scale; MBP 5 myelin basic protein; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; NMOSD 5 NMO spectrum disorder; OCB 5 oligoclonal band; ON 5 optic neuritis; OPC 5 oligodendrocyte precursor cell; TM 5 transverse myelitis.There is presently limited insight into the pathophysiologic mechanisms underlying childhoodonset inflammatory demyelinating diseases. Because these disorders occur in the context of the developing immune and nervous systems, understanding the implications to both disease mechanisms and efficacy and safety profiles of potential therapeutics will help guide optimal management approaches for these children and adolescents. Elucidating the biology of pediatric-onset multiple sclerosis (MS) may provide key insights into earliest targets and processes involved in disease pathogenesis as well as into the broader spectrum of CNS...

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Section: Cns-directed Antibodies In Pediatricmentioning

confidence: 99%

Section: Cns-directed Antibodies In Pediatricmentioning

confidence: 99%

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

et al. 2016

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“…7 We recently reported a remarkable elevation of myelin basic protein without glial fibrillary acidic protein detectable in the CSF of a patient with anti-MOG+ definitive NMO, suggesting myelin damage without astrocyte injury. 8 In common, both cases had anti-MOG positivity at the first event without any previous manifestation to induce exposition of central nervous system (CNS) antigens promoting a bystander phenomenon to produce autoantibodies.…”

Section: Discussionmentioning

confidence: 91%

Anti-MOG (Myelin Oligodendrocyte Glycoprotein)–Positive Severe Optic Neuritis with Optic Disc Ischaemia and Macular Star

Moura

Sato

Rimkus

et al. 2015

Neuro-Ophthalmology

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A 44-year-old man presented with severe right visual loss. The right fundus examination showed marked optic disc oedema associated with partial macular star. Serological blood tests for infectious agents were all negative. Serum aquaporin-4 antibody was negative but anti-MOG (myelin oligodendrocyte glycoprotein) was positive. Magnetic resonance revealed extensive lesion in right optic nerve. There was no visual improvement after intravenous therapy. Patient had no further attacks after follow-up. Optic disc oedema with macular star is found in several infectious and non-inflammatory disorders, but it has not been reported in optic neuritis (ON) associated with autoantibodies to myelin oligodendrocyte glycoprotein (anti-MOG).

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“…(7/22), further strengthening the case that MOG antibody supports a non-MS diagnosis, although larger cohorts are required to further test this association. 30 Another study evaluated the frequencies of 57 of the newly identified non-HLA MS risk single nucleotide polymorphisms (SNPs) in 188 children with ADS, of whom 53 individuals had a subsequent diagnosis of MS. 31 In order to control the effect of genetic variation due to ancestry, only patients with European ancestry were included. Control groups were 456 patients with adult MS and 2,046 healthy adults.…”

Section: Genetic Background Associated Withmentioning

confidence: 99%

Pediatric acquired CNS demyelinating syndromes

et al. 2016

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Approximately one-third of children with an acquired demyelinating syndrome (ADS) will be diagnosed with multiple sclerosis (MS), either at onset according to the 2010 McDonald criteria, or on the basis of clinical or MRI evidence of relapsing disease, in the majority of patients within 2-4 years. ADS in adolescents, female patients, and patients with polyfocal deficits is associated with the highest likelihood of MS, while children with acute disseminated encephalomyelitis, those with documented preceding infection, and ADS presentation in young children more commonly portends a monophasic outcome. While pediatric MS associates with similar genetic risk alleles as have been documented in adult-onset MS, such associations are not diagnostically valuable at the individual level. The presence of antibodies directed against aquaporin-4 strongly supports a diagnosis of neuromyelitis optica, and should be assayed in children manifesting with severe optic neuritis, longitudinally extensive myelitis, or brainstem/hypothalamic syndromes. Further research will determine whether other antibody signatures are indicative of relapsing demyelination distinct from MS. Neurology ® 2016;87 (Suppl 2):S67-S73 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; ADS 5 acquired demyelinating syndromes; CI 5 confidence interval; CIS 5 clinically isolated syndrome; HLA 5 human leukocyte antigen; HR 5 hazard ratio; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; NPV 5 negative predictive value; OCB 5 oligoclonal band; ON 5 optic neuritis; OR 5 odds ratio; PPV 5 positive predictive value; SNP 5 single nucleotide polymorphism; TM 5 transverse myelitis.

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Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton

Cited by 154 publications

References 38 publications

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

Anti-MOG (Myelin Oligodendrocyte Glycoprotein)–Positive Severe Optic Neuritis with Optic Disc Ischaemia and Macular Star

Pediatric acquired CNS demyelinating syndromes

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