Highlights
- •MOG-Ab associated disease is more common in children than in adults.
- •We examined MOG-Ab status in our pediatric multiple sclerosis (pMS) cases.
- •MOG-Ab positivity in our pMS series was similar to rates reported in adult MS.
- •Relapse rate was low and course was similar in MOG-Ab positive and negative pMS cases.
Abstract
Background
Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are associated with acute
demyelinating syndromes and only rarely detected in multiple sclerosis (MS). As MOG-Ab
associated disease is common in childhood, we speculated young patients might be more
likely to produce MOG-Ab and investigated the frequency of MOG-Ab seropositivity in
pediatric onset MS (POMS).
Material and methods
Patients who experienced their first acute demyelinating event before age 18 years
and were diagnosed with MS during follow-up were included in this single-center study.
Patient data were retrieved from clinical records. Serum samples obtained and frozen
at clinical visits were analyzed for MOG-Ab by a live cell-based assay (CBA) measuring
delta mean fluorescence intensity (MFI) and MFI ratio. The control group consisted
of patients referred to pediatric neurology for headache or vertigo and who had no
neurological disorder (n = 48). Another control group consisted of patients with systemic inflammatory disorders
systemic lupus erythematosus (n = 17) and juvenile idiopathic arthritis (n = 13) diagnosed in the rheumatology clinic.
Results
The patient group (n = 122, F/M: 90/32, mean age 17.8 ± 2.6 years) were initially diagnosed as: MS, 62/122
(50.8%), clinically isolated syndrome, 43/122 (35.2%), radiologically isolated syndrome,
9/122 (7.3%), and acute disseminated encephalomyelitis 8/122 (6.5%). All received
the final diagnosis of POMS. Serum was sampled 22.4 ± 29.2 (0–132) months after the
first episode. None of the control groups had MOG-Ab positivity while 2/122 (1.6%)
POMS cases had MOG-Abs, and a third patient had positive MFI and a MFI ratio slightly
below the cut-off. These three patients’ initial and final diagnoses were MS, their
annualized relapsing rates (ARRs) were 0.4–0.6, and most recent Expanded Disability
Status Scale was 0.
Conclusion
Low titers of MOG-Ab can be detected in a small number of POMS patients at similar
frequency with adult MS. Our POMS cases with MOG-Abs presented brainstem-cerebellar
findings or seizures and had low ARR. Further series and longer follow-up will define
whether these cases differ significantly from MOG-Ab negative POMS cases.
Keywords
Abbreviations:
MS (multiple sclerosis), HC (healthy control), JIA (juvenile idiopathic arthritis), SLE (systemic lupus erythematosus), MFI (mean of fluorescence intensity), MOG-Ab (myelin oligodendrocyteglycoprotein antibody)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- E.U. paediatric MOG consortium consensus: part 3 - biomarkers of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.Eur. J. Paediatr. Neurol. 2020; 29: 22-31
- Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study.Lancet Neurol. 2020; 19: 234-246
- E.U. paediatric MOG consortium consensus: part 1 - classification of clinical phenotypes of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.Eur. J. Paediatr. Neurol. 2020; 29: 2-13
- Frequency of myelin oligodendrocyte glycoprotein antibody in multiple sclerosis: a multicenter cross-sectional study.Neurol. Neuroimmunol. Neuroinflamm. 2020; 7: e649
- Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study.Neurology. 2018; 90: e1858-e1e69
- The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults.Mult. Scler. 2020; 26: 806-814
- Serum MOG-IgG in children meeting multiple sclerosis diagnostic criteria.Mult. Scler. J. 2022; (In press)
- MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines.Lancet Neurol. 2016; 15: 292-303
- Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children.Neurol. Neuroimmunol. Neuroinflamm. 2015; 2: e81
- Seizures and encephalitis in myelin oligodendrocyte glycoprotein IgG disease vs aquaporin 4 IgG disease.JAMA Neurol. 2018; 75: 65-71
- New concepts in the immunopathogenesis of multiple sclerosis.Nat. Rev. Neurosci. 2002; 3: 291-301
- Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome.Neurology. 2017; 89: 900-908
- Myelin oligodendrocyte glycoprotein antibody associated central nervous system demyelinating disease: a tertiary center experience from Turkey.Mult. Scler. Relat. Disord. 2020; 44102376
- Clinical presentation and prognosis in MOG-antibody disease: a UK study.Brain. 2017; 140: 3128-3138
- Anti-myelin oligodendrocyte glycoprotein B-cell responses in multiple sclerosis.J. Neuroimmunol. 2003; 135: 117-125
- Anti-MOG antibodies plead against MS diagnosis in an acquired demyelinating syndromes cohort.Mult. Scler. 2015; 21: 1513-1520
- Epitope specificity of serum antibodies directed against the extracellular domain of myelin oligodendrocyte glycoprotein: influence of relapses and immunomodulatory treatments.J. Neuroimmunol. 2006; 174: 147-156
- International pediatric multiple sclerosis study group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions.Mult. Scler. 2013; 19: 1261-1267
- Myelin oligodendrocyte glycoprotein-immunoglobulin G in the CSF: clinical implication of testing and association with disability.Neurol. Neuroimmunol. Neuroinflamm. 2022; 9: e1095
- Features of MOG required for recognition by patients with MOG antibody-associated disorders.Brain. 2021; 144: 2375-2389
- Myelin-oligodendrocyte glycoprotein antibody-associated disease.Lancet Neurol. 2021; 20: 762-772
- Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study.J. Neurol. 2017; 264: 2420-2430
- Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein.Nat. Med. 2007; 13: 211-217
- MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy.Neurol. Neuroimmunol. Neuroinflamm. 2017; 4: e322
- The spectrum of MOG autoantibody-associated demyelinating diseases.Nat. Rev. Neurol. 2013; 9: 455-461
- Myelin oligodendrocyte glycoprotein antibodies in neurological disease.Nat. Rev. Neurol. 2019; 15: 89-102
- Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis.Neurol. Neuroimmunol. Neuroinflamm. 2016; 3: e257
- Histopathology and clinical course of MOG-antibody-associated encephalomyelitis.Ann. Clin. Transl. Neurol. 2015; 2: 295-301
- Serial anti-myelin oligodendrocyte glycoprotein antibody analyses and outcomes in children with demyelinating syndromes.JAMA Neurol. 2020; 77: 82-93
Article info
Publication history
Published online: August 08, 2022
Accepted:
August 7,
2022
Received in revised form:
May 29,
2022
Received:
January 3,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
