Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort

Ketelslegers, Immy A.; Pelt, Daniëlle E. van; Bryde, Susanne; Neuteboom, Rinze F.; Catsman‐Berrevoets, Coriene E.; Hamann, Dörte; Hintzen, Rogier Q.

doi:10.1177/1352458514566666

Cited by 166 publications

(159 citation statements)

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“…These children with a multiphasic disease course often have ADEM followed by one or more ON. 24,26 Similar results have been documented by other groups, 25 indicating that the presence of anti-MOG positivity tested with cell-based assays statistically suggests against a diagnosis of MS. Still, other studies using cell-based assays have found anti-MOG antibodies particularly in children diagnosed with MS younger than 10 years, 27 suggesting an age-dependent presence of MOG antibodies in pediatric MS.…”

Section: Serum Antibodies To Myelin Oligodendro-cyte Glycoprotein (Mog)supporting

confidence: 76%

“…A Dutch nationwide cohort study on 117 children with ADS showed that patients with ADS with antibodies to MOG more frequently present with a polyfocal disease onset with or without encephalopathy, next to TM (recurrent), ON, or NMO negative for antibodies to aquaporin-4. 24 Children with multiphasic ADS not fulfilling MS diagnostic criteria were likely to be positive (8/11) for anti-MOG antibodies. These children with a multiphasic disease course often have ADEM followed by one or more ON.…”

Section: Serum Antibodies To Myelin Oligodendro-cyte Glycoprotein (Mog)mentioning

confidence: 99%

“…[24][25][26] The percentage of anti-MOG antibody-positive patients within these ADS groups ranges between 12% and 35%. Children with antibodies to MOG are typically younger than children without antibodies to MOG.…”

Section: Serum Antibodies To Myelin Oligodendro-cyte Glycoprotein (Mog)mentioning

confidence: 99%

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Pediatric acquired CNS demyelinating syndromes

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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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Section: Serum Antibodies To Myelin Oligodendro-cyte Glycoprotein (Mog)supporting

confidence: 76%

Section: Serum Antibodies To Myelin Oligodendro-cyte Glycoprotein (Mog)mentioning

confidence: 99%

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Pediatric acquired CNS demyelinating syndromes

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“…43 Compared to AQP4 IgG-associated disease, CBA seropositivity for MOG IgG appears to be associated with less severe disease, including better resolution and less likelihood to relapse, 44 and may also be associated with a non-MS disease phenotype. 45 A serum antibody binding to KIR4.1 (the ATPsensitive inward rectifying potassium channel found primarily on glial cells) has been reported in 47% of adults with MS as well as in a subset of children with acute CNS demyelination. 46,47 Presence of this antibody was not associated with particular clinical features and its significance is uncertain at this time.…”

Section: Cns-directed Antibodies In Pediatricmentioning

confidence: 99%

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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“…There is some preliminary evidence suggesting potential pathogenicity. 13,14 Pooled data suggest that 25% of children with acute demyelination have MOG antibodies, and the presence of such anti-MOG antibodies occurs in ADEM, recurrent optic neuritis, in some children with AQP4-negative NMOSD, and less commonly in children experiencing the first attack of MS. 15,16 The spectrum of MOGassociated diseases in childhood needs to be further defined and more research is required to determine diagnostic and therapeutic implications.…”

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confidence: 99%

International Pediatric MS Study Group Global Members Symposium report

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The International Pediatric Multiple Sclerosis Study Group held its inaugural educational program, "The World of Pediatric MS: A Global Update," in September 2014 to discuss advances and challenges in the diagnosis and management of pediatric multiple sclerosis (MS) and other neuroinflammatory CNS disorders. Highlights included a discussion on the revised diagnostic criteria, which enable the differentiation of MS, acute disseminated encephalomyelitis, neuromyelitis optica, and other neuroinflammatory disorders. While these criteria currently identify clinical and MRI features for a particular diagnosis, advances in biomarkers may prove to be useful in the future. An update was also provided on environmental factors associated with pediatric MS risk and possibly outcomes, notably vitamin D deficiency. However, optimal vitamin D intake and its role in altering MS course in children have yet to be established. Regarding MS outcomes, our understanding of the cognitive consequences of early-onset MS has grown. However, further work is needed to define the course of cognitive function and its long-term outcome in diverse patient samples and to develop strategies for effective cognitive rehabilitation specifically tailored to children and adolescents. Finally, treatment strategies were discussed, including a need to consider additional drug treatment options and paradigms (escalation vs induction), although treatment should be tailored to the individual child. Of critical importance, clinical trials of newer MS agents in children are required. Although our understanding of childhood MS has improved, further research is needed to have a positive impact for children and their families. Neurology ® 2016;87 (Suppl 2):S110-S116 GLOSSARY ADEM 5 acute disseminated encephalomyelitis; ADS 5 acute demyelinating syndrome; AQP4 5 aquaporin-4; CI 5 confidence interval; CIS 5 clinically isolated syndrome; DMT 5 disease-modifying treatment; EDSS 5 Expanded Disability Status Scale; EMA 5 European Medicines Agency; FDA 5 Food and Drug Administration; IPMSSG 5 International Pediatric MS Study Group; MOG 5 myelin oligodendrocyte glycoprotein; MS 5 multiple sclerosis; NMO 5 neuromyelitis optica; NMOSD 5 neuromyelitis optica spectrum disorder; RDA 5 Recommended Dietary Allowance.Advances in our understanding of epidemiology, pathogenesis, and treatment in multiple sclerosis (MS) have been rapid in the last few years and will have a positive effect for children with the disease. Such progress in the diagnosis and management of pediatric MS and neuroinflammatory disorders includes the following:1. Revised diagnostic criteria for MS, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica (NMO) across the age spectrum. 2. Improved understanding of the cognitive consequences of MS onset during childhood. 3. Additional drug treatment options, including immunosuppressant, immunomodulatory, and oral medications, and awareness of the need for clinical trials of these agents in children.

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Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort

Abstract: MOG antibodies are strongly skewed towards ADS children that present with an ADEM-like disease onset. The presence of such antibodies pleads against a future diagnosis of MS.

Cited by 166 publications

References 32 publications

Pediatric acquired CNS demyelinating syndromes

Pediatric acquired CNS demyelinating syndromes

Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases

International Pediatric MS Study Group Global Members Symposium report

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