Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Myelin oligodendrocyte glycoprotein antibodies in neurological disease

Nature Reviews Neurology volume 15, pages 89–102 (2019)Cite this article

Subjects

Abstract

Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-Abs) were first detected by immunoblot and enzyme-linked immunosorbent assay nearly 30 years ago, but their association with multiple sclerosis (MS) was not specific. Use of cell-based assays with native MOG as the substrate enabled identification of a group of MOG-Ab-positive patients with demyelinating phenotypes. Initially, MOG-Abs were reported in children with acute disseminated encephalomyelitis (ADEM). Further studies identified MOG-Abs in adults and children with ADEM, seizures, encephalitis, anti-aquaporin-4-antibody (AQP4-Ab)-seronegative neuromyelitis optica spectrum disorder (NMOSD) and related syndromes (optic neuritis, myelitis and brainstem encephalitis), but rarely in MS. This shift in our understanding of the diagnostic assays has re-invigorated the examination of MOG-Abs and their role in autoimmune and demyelinating disorders of the CNS. The clinical phenotypes, disease courses and responses to treatment that are associated with MOG-Abs are currently being defined. MOG-Ab-associated disease is different to AQP4-Ab-positive NMOSD and MS. This Review provides an overview of the current knowledge of MOG, the metrics of MOG-Ab assays and the clinical associations identified. We collate the data on antibody pathogenicity and the mechanisms that are thought to underlie this. We also highlight differences between MOG-Ab-associated disease, NMOSD and MS, and describe our current understanding on how best to treat MOG-Ab-associated disease.

Key points

  • Antibodies against myelin oligodendrocyte glycoprotein (MOG-Abs) that are detectable with cell-based assays are associated with non-MS acquired demyelinating syndromes of the CNS.

  • MOG-Ab-associated disorders account for a larger proportion of paediatric patients than that of adult patients who present with acquired demyelinating disease.

  • The clinical presentation of MOG-Ab-associated disorders changes with age: MOG-Abs are associated with an ADEM-like presentation in young children and an opticospinal presentation in children aged >9 years and adults.

  • Most patients with MOG-Ab-associated disorders have favourable outcomes, but a subset are left with permanent disability, usually as a result of the initial attack.

  • Many patients develop relapsing disease; relapses usually involve optic neuritis and often occur during steroid weaning or soon after steroid cessation, suggesting that a longer initial treatment duration is required.

  • Investigation of human MOG-Ab pathogenicity is hampered by their limited binding to rodent MOG; nevertheless, the place of MOG-Ab-associated disorders in the spectrum of inflammatory demyelinating diseases is becoming clearer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The structures and functions of myelin oligodendrocyte glycoprotein isoforms.
Fig. 2: Anti-MOG antibodies are associated with anti-aquaporin-4-antibody-negative non-multiple sclerosis demyelinating diseases.
Fig. 3: The seroprevalence and clinical presentations associated with anti-MOG antibodies are age-dependent.

Similar content being viewed by others

References

  1. Lebar, R., Baudrimont, M. & Vincent, C. Chronic experimental autoimmune encephalomyelitis in the guinea pig. Presence of anti-M2 antibodies in central nervous system tissue and the possible role of M2 autoantigen in the induction of the disease. J. Autoimmun. 2, 115–132 (1989).

    CAS  PubMed  Google Scholar 

  2. Linington, C., Bradl, M., Lassmann, H., Brunner, C. & Vass, K. Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am. J. Pathol. 130, 443–454 (1988). The first demonstration of the pathogenicity of MOG-Abs.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Brunner, C., Lassmann, H., Waehneldt, T. V., Matthieu, J. M. & Linington, C. Differential ultrastructural localization of myelin basic protein, myelin/oligodendroglial glycoprotein, and 2ʹ,3ʹ-cyclic nucleotide 3ʹ-phosphodiesterase in the CNS of adult rats. J. Neurochem. 52, 296–304 (1989).

    CAS  PubMed  Google Scholar 

  4. Pham-Dinh, D. et al. Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex. Proc. Natl Acad. Sci. USA 90, 7990–7994 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Delarasse, C. et al. Complex alternative splicing of the myelin oligodendrocyte glycoprotein gene is unique to human and non-human primates. J. Neurochem. 98, 1707–1717 (2006).

    CAS  PubMed  Google Scholar 

  6. Kang, H. J. et al. Spatio-temporal transcriptome of the human brain. Nature 478, 483–489 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Boyle, L. H., Traherne, J. A., Plotnek, G., Ward, R. & Trowsdale, J. Splice variation in the cytoplasmic domains of myelin oligodendrocyte glycoprotein affects its cellular localisation and transport. J. Neurochem. 102, 1853–1862 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Marta, C. B. et al. Signaling cascades activated upon antibody cross-linking of myelin oligodendrocyte glycoprotein: potential implications for multiple sclerosis. J. Biol. Chem. 280, 8985–8993 (2005).

    CAS  PubMed  Google Scholar 

  9. Johns, T. G. & Bernard, C. C. The structure and function of myelin oligodendrocyte glycoprotein. J. Neurochem. 72, 1–9 (1999).

    CAS  PubMed  Google Scholar 

  10. von Budingen, H. C. et al. The myelin oligodendrocyte glycoprotein directly binds nerve growth factor to modulate central axon circuitry. J. Cell Biol. 210, 891–898 (2015).

    Google Scholar 

  11. Cong, H., Jiang, Y. & Tien, P. Identification of the myelin oligodendrocyte glycoprotein as a cellular receptor for rubella virus. J. Virol. 85, 11038–11047 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Garcia-Vallejo, J. J. et al. CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG. J. Exp. Med. 211, 1465–1483 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Delarasse, C. et al. Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice. J. Clin. Invest. 112, 544–553 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Linares, D. et al. The magnitude and encephalogenic potential of autoimmune response to MOG is enhanced in MOG deficient mice. J. Autoimmun. 21, 339–351 (2003).

    CAS  PubMed  Google Scholar 

  15. Iglesias, A., Bauer, J., Litzenburger, T., Schubart, A. & Linington, C. T- and B cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36, 220–234 (2001).

    CAS  PubMed  Google Scholar 

  16. Peschl, P., Bradl, M., Hoftberger, R., Berger, T. & Reindl, M. Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases. Front. Immunol. 8, 529 (2017).

    PubMed  PubMed Central  Google Scholar 

  17. Karni, A., Bakimer-Kleiner, R., Abramsky, O. & Ben-Nun, A. Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis. Arch. Neurol. 56, 311–315 (1999).

    CAS  PubMed  Google Scholar 

  18. Lindert, R. B. et al. Multiple sclerosis: B− and T cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein. Brain 122, 2089–2100 (1999).

    PubMed  Google Scholar 

  19. Reindl, M. et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain 122, 2047–2056 (1999).

    PubMed  Google Scholar 

  20. Egg, R., Reindl, M., Deisenhammer, F., Linington, C. & Berger, T. Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis. Mult. Scler. 7, 285–289 (2001).

    CAS  PubMed  Google Scholar 

  21. Schmidt, S. et al. Serum autoantibody responses to myelin oligodendrocyte glycoprotein and myelin basic protein in X-linked adrenoleukodystrophy and multiple sclerosis. J. Neuroimmunol. 119, 88–94 (2001).

    CAS  PubMed  Google Scholar 

  22. Lutterotti, A. et al. Antibody response to myelin oligodendrocyte glycoprotein and myelin basic protein depend on familial background and are partially associated with human leukocyte antigen alleles in multiplex families and sporadic multiple sclerosis. J. Neuroimmunol. 131, 201–207 (2002).

    CAS  PubMed  Google Scholar 

  23. Berger, T. et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N. Engl. J. Med. 349, 139–145 (2003).

    CAS  PubMed  Google Scholar 

  24. Mantegazza, R. et al. Anti-MOG autoantibodies in Italian multiple sclerosis patients: specificity, sensitivity and clinical association. Int. Immunol. 16, 559–565 (2004).

    CAS  PubMed  Google Scholar 

  25. O’Connor, K. C. et al. Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein. J. Immunol. 175, 1974–1982 (2005).

    PubMed  Google Scholar 

  26. Pittock, S. J. et al. Anti-myelin antibodies: frequency, stability and clinicopathologic associations in a biopsy MS cohort. Mult. Scler. 11, 109–109 (2005).

    Google Scholar 

  27. Kuhle, J. et al. Lack of association between antimyelin antibodies and progression to multiple sclerosis. N. Engl. J. Med. 356, 371–378 (2007).

    CAS  PubMed  Google Scholar 

  28. O’Connor, K. C. et al. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat. Med. 13, 211–217 (2007).

    PubMed  PubMed Central  Google Scholar 

  29. Wang, H. et al. Myelin oligodendrocyte glycoprotein antibodies and multiple sclerosis in healthy young adults. Neurology 71, 1142–1146 (2008).

    CAS  PubMed  Google Scholar 

  30. Di Pauli, F. et al. Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases. Clin. Immunol. 138, 247–254 (2011). The first study in which CBA-IF was used for the detection of MOG-Abs.

    PubMed  Google Scholar 

  31. Lalive, P. H. et al. Highly reactive anti-myelin oligodendrocyte glycoprotein antibodies differentiate demyelinating diseases from viral encephalitis in children. Mult. Scler. 17, 297–302 (2011).

    CAS  PubMed  Google Scholar 

  32. Menge, T., Lalive, P. H., von Budingen, H. C. & Genain, C. P. Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis. J. Neuroinflamm. 8, 161 (2011).

    CAS  Google Scholar 

  33. Lackner, P. et al. Antibodies to myelin oligodendrocyte glycoprotein in HIV-1 associated neurocognitive disorder: a cross-sectional cohort study. J. Neuroinflamm. 7, 79 (2010).

    Google Scholar 

  34. Kezuka, T. et al. Relationship between NMO-antibody and anti-MOG antibody in optic neuritis. J. Neuroophthalmol. 32, 107–110 (2012).

    PubMed  Google Scholar 

  35. Wingerchuk, D. M., Lennon, V. A., Pittock, S. J., Lucchinetti, C. F. & Weinshenker, B. G. Revised diagnostic criteria for neuromyelitis optica. Neurology 66, 1485–1489 (2006).

    CAS  PubMed  Google Scholar 

  36. Lampasona, V. et al. Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects. Neurology 62, 2092–2094 (2004).

    CAS  PubMed  Google Scholar 

  37. Waters, P., Pettingill, P. & Lang, B. Detection methods for neural autoantibodies. Handb. Clin. Neurol. 133, 147–163 (2016).

    PubMed  Google Scholar 

  38. Rogers, S. W. et al. Autoantibodies to glutamate receptor GluR3 in Rasmussen’s encephalitis. Science 265, 648–651 (1994).

    CAS  PubMed  Google Scholar 

  39. Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S. & Hinson, S. R. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J. Exp. Med. 202, 473–477 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Haase, C. G. et al. The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls. J. Neuroimmunol. 114, 220–225 (2001).

    CAS  PubMed  Google Scholar 

  41. Lalive, P. H. et al. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis. Proc. Natl Acad. Sci. USA 103, 2280–2285 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhou, D. et al. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis. Proc. Natl Acad. Sci. USA 103, 19057–19062 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Brilot, F. et al. Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann. Neurol. 66, 833–842 (2009). One of the studies in which a CBA-FACS assay for detection of MOG-Abs was established.

    CAS  PubMed  Google Scholar 

  44. McLaughlin, K. A. et al. Age-dependent B cell autoimmunity to a myelin surface antigen in pediatric multiple sclerosis. J. Immunol. 183, 4067–4076 (2009). One of the studies in which a CBA-FACS assay for detection of MOG-Abs was established.

    CAS  PubMed  Google Scholar 

  45. Waters, P. et al. MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol. Neuroimmunol. Neuroinflamm. 2, e89 (2015). A study in which a novel assay for IgG1 MOG-Abs was established.

    PubMed  PubMed Central  Google Scholar 

  46. Dahm, L. et al. Seroprevalence of autoantibodies against brain antigens in health and disease. Ann. Neurol. 76, 82–94 (2014).

    CAS  PubMed  Google Scholar 

  47. Ramberger, M. et al. Comparison of diagnostic accuracy of microscopy and flow cytometry in evaluating N-methyl-D-aspartate receptor antibodies in serum using a live cell-based assay. PLOS ONE 10, e0122037 (2015).

    PubMed  PubMed Central  Google Scholar 

  48. Probstel, A. K. et al. Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype. J. Neuroinflamm. 12, 46 (2015).

    Google Scholar 

  49. Yan, Y. et al. Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD. Sci. China Life Sci. 59, 1270–1281 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. van Pelt, E. D., Wong, Y. Y., Ketelslegers, I. A., Hamann, D. & Hintzen, R. Q. Neuromyelitis optica spectrum disorders: comparison of clinical and magnetic resonance imaging characteristics of AQP4-IgG versus MOG-IgG seropositive cases in the Netherlands. Eur. J. Neurol. 23, 580–587 (2016).

    PubMed  Google Scholar 

  51. Jitprapaikulsan, J. et al. Aquaporin-4 and myelin oligodendrocyte glycoprotein autoantibody status predict outcome of recurrent optic neuritis. Ophthalmology 125, 1628–1637 (2018).

    PubMed  Google Scholar 

  52. Jitprapaikulsan, J. et al. Novel glial targets and recurrent longitudinally extensive transverse myelitis. JAMA Neurol. 75, 892–895 (2018).

    PubMed  PubMed Central  Google Scholar 

  53. Mader, S. et al. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J. Neuroinflamm. 8, 184 (2011). The first study to demonstrate the presence of MOG-Abs in NMOSD.

    CAS  Google Scholar 

  54. Kitley, J. et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 79, 1273–1277 (2012).

    CAS  PubMed  Google Scholar 

  55. Woodhall, M. et al. Glycine receptor and myelin oligodendrocyte glycoprotein antibodies in Turkish patients with neuromyelitis optica. J. Neurol. Sci. 335, 221–223 (2013).

    CAS  PubMed  Google Scholar 

  56. Kitley, J. et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol. 71, 276–283 (2014). One of the initial studies of MOG-Abs in NMOSD.

    PubMed  Google Scholar 

  57. Sato, D. K. et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 82, 474–481 (2014). One of the initial studies of MOG-Abs in NMOSD.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Tanaka, M. & Tanaka, K. Anti-MOG antibodies in adult patients with demyelinating disorders of the central nervous system. J. Neuroimmunol. 270, 98–99 (2014).

    CAS  PubMed  Google Scholar 

  59. Hacohen, Y. et al. Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children. Neurol. Neuroimmunol. Neuroinflamm. 2, e81 (2015).

    PubMed  PubMed Central  Google Scholar 

  60. Hoftberger, R. et al. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult. Scler. 21, 866–874 (2015).

    CAS  PubMed  Google Scholar 

  61. Kim, S. M. et al. Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS. Neurol. Neuroimmunol. Neuroinflamm. 2, e163 (2015).

    PubMed  PubMed Central  Google Scholar 

  62. Martinez-Hernandez, E. et al. Antibodies to aquaporin 4, myelin-oligodendrocyte glycoprotein, and the glycine receptor alpha1 subunit in patients with isolated optic neuritis. JAMA Neurol. 72, 187–193 (2015).

    PubMed  PubMed Central  Google Scholar 

  63. Ramberger, M. et al. NMDA receptor antibodies: a rare association in inflammatory demyelinating diseases. Neurol. Neuroimmunol. Neuroinflamm. 2, e141 (2015).

    PubMed  PubMed Central  Google Scholar 

  64. Jarius, S. et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J. Neuroinflamm. 13, 279 (2016). One of the largest analyses of MOG-Abs in NMOSD.

    Google Scholar 

  65. Piccolo, L. et al. Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up. J. Neurol. 263, 370–379 (2016).

    CAS  PubMed  Google Scholar 

  66. Sepulveda, M. et al. Neuromyelitis optica spectrum disorders: comparison according to the phenotype and serostatus. Neurol. Neuroimmunol. Neuroinflamm. 3, e225 (2016).

    PubMed  PubMed Central  Google Scholar 

  67. Siritho, S., Sato, D. K., Kaneko, K., Fujihara, K. & Prayoonwiwat, N. The clinical spectrum associated with myelin oligodendrocyte glycoprotein antibodies (anti-MOG-Ab) in Thai patients. Mult. Scler. 22, 964–968 (2016).

    CAS  PubMed  Google Scholar 

  68. Hamid, S. H. M. et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J. Neurol. 264, 2088–2094 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Hyun, J. W. et al. Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases. J. Neurol. Neurosurg. Psychiatry 88, 811–817 (2017).

    PubMed  Google Scholar 

  70. Sepulveda, M. et al. Epidemiology of NMOSD in Catalonia: influence of the new 2015 criteria in incidence and prevalence estimates. Mult. Scler. https://doi.org/10.1177/1352458517735191 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Duignan, S. et al. Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly specific in children with acquired demyelinating syndromes. Dev. Med. Child Neurol. 60, 958–962 (2018).

    PubMed  Google Scholar 

  72. Mader, S. et al. Understanding the antibody repertoire in neuropsychiatric systemic lupus erythematosus and neuromyelitis optica spectrum disorder: do they share common targets? Arthritis Rheumatol. 70, 277–286 (2018).

    CAS  PubMed  Google Scholar 

  73. Titulaer, M. J. et al. Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann. Neurol. 75, 411–428 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Zhou, L. et al. MOG-antibody associated demyelinating disease of the CNS: a clinical and pathological study in Chinese Han patients. J. Neuroimmunol. 305, 19–28 (2017).

    CAS  PubMed  Google Scholar 

  75. Zhao, G. et al. Clinical characteristics of myelin oligodendrocyte glycoprotein seropositive optic neuritis: a cohort study in Shanghai, China. J. Neurol. 265, 33–40 (2018).

    CAS  PubMed  Google Scholar 

  76. Rostasy, K. et al. Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica. Mult. Scler. 19, 1052–1059 (2013).

    CAS  PubMed  Google Scholar 

  77. Chalmoukou, K. et al. Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis. Neurol. Neuroimmunol. Neuroinflamm. 2, e131 (2015).

    PubMed  PubMed Central  Google Scholar 

  78. Elong Ngono, A. et al. Decreased frequency of circulating myelin oligodendrocyte glycoprotein B lymphocytes in patients with relapsing-remitting multiple sclerosis. J. Immunol. Res. 2015, 673503 (2015).

    PubMed  PubMed Central  Google Scholar 

  79. Hacohen, Y. et al. Diagnostic algorithm for relapsing acquired demyelinating syndromes in children. Neurology 89, 269–278 (2017). One of the largest studies of MOG-Abs in children.

    PubMed  Google Scholar 

  80. Hennes, E. M. et al. Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology 89, 900–908 (2017). One of the largest studies of MOG-Abs in children.

    CAS  PubMed  Google Scholar 

  81. Mariotto, S. et al. Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study. J. Neurol. 264, 2420–2430 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Soelberg, K. et al. A population-based prospective study of optic neuritis. Mult. Scler. 23, 1893–1901 (2017).

    CAS  PubMed  Google Scholar 

  83. Jarius, S. et al. MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature. J. Neuroinflamm. 15, 88 (2018).

    CAS  Google Scholar 

  84. Rostasy, K. et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis. Arch. Neurol. 69, 752–756 (2012).

    PubMed  Google Scholar 

  85. Jarius, S. et al. Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in ‘pattern II multiple sclerosis’ and brain biopsy findings in a MOG-IgG-positive case. Mult. Scler. 22, 1541–1549 (2016).

    CAS  PubMed  Google Scholar 

  86. Cobo-Calvo, A. et al. MOG antibody-related disorders: common features and uncommon presentations. J. Neurol. 264, 1945–1955 (2017).

    CAS  PubMed  Google Scholar 

  87. Thompson, A. J. et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 17, 162–173 (2018).

    PubMed  Google Scholar 

  88. Chen, J. J. et al. Prevalence of myelin oligodendrocyte glycoprotein and aquaporin-4-IgG in patients in the Optic Neuritis Treatment Trial. JAMA Ophthalmol. 136, 419–422 (2018).

    PubMed  PubMed Central  Google Scholar 

  89. Dale, R. C. et al. Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton. Neurol. Neuroimmunol. Neuroinflamm. 1, e12 (2014).

    PubMed  PubMed Central  Google Scholar 

  90. de Mol, C. L. et al. Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study. J. Neurol. 265, 1310–1319 (2018). One of the largest studies of MOG-Abs in children.

    PubMed  PubMed Central  Google Scholar 

  91. Fernandez-Carbonell, C. et al. Clinical and MRI phenotype of children with MOG antibodies. Mult. Scler. 22, 174–184 (2016).

    CAS  PubMed  Google Scholar 

  92. Ketelslegers, I. A. et al. Anti-MOG antibodies plead against MS diagnosis in an acquired demyelinating syndromes cohort. Mult. Scler. 21, 1513–1520 (2015).

    CAS  PubMed  Google Scholar 

  93. Probstel, A. K. et al. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 77, 580–588 (2011).

    CAS  PubMed  Google Scholar 

  94. Ramanathan, S. et al. Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis. Neurol. Neuroimmunol. Neuroinflamm. 1, e40 (2014).

    PubMed  PubMed Central  Google Scholar 

  95. Selter, R. C. et al. Antibody responses to EBV and native MOG in pediatric inflammatory demyelinating CNS diseases. Neurology 74, 1711–1715 (2010).

    CAS  PubMed  Google Scholar 

  96. Lopez-Chiriboga, A. S. et al. Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2018.1814 (2018). A large study on MOG-Abs in ADEM.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Hacohen, Y. et al. Autoantibody biomarkers in childhood-acquired demyelinating syndromes: results from a national surveillance cohort. J. Neurol. Neurosurg. Psychiatry 85, 456–461 (2014).

    PubMed  Google Scholar 

  98. Cobo-Calvo, A. et al. Antibodies to myelin oligodendrocyte glycoprotein in aquaporin 4 antibody seronegative longitudinally extensive transverse myelitis: clinical and prognostic implications. Mult. Scler. 22, 312–319 (2016).

    CAS  PubMed  Google Scholar 

  99. Bouzar, M. et al. Neuromyelitis optica spectrum disorders with antibodies to myelin oligodendrocyte glycoprotein or aquaporin-4: clinical and paraclinical characteristics in Algerian patients. J. Neurol. Sci. 381, 240–244 (2017).

    CAS  PubMed  Google Scholar 

  100. Hacohen, Y. et al. Paediatric brainstem encephalitis associated with glial and neuronal autoantibodies. Dev. Med. Child Neurol. 58, 836–841 (2016).

    PubMed  Google Scholar 

  101. Baumann, M. et al. Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J. Neurol. Neurosurg. Psychiatry 86, 265–272 (2015). A large study of MOG-Abs in ADEM.

    CAS  PubMed  Google Scholar 

  102. Lechner, C. et al. Antibodies to MOG and AQP4 in children with neuromyelitis optica and limited forms of the disease. J. Neurol. Neurosurg. Psychiatry 87, 897–905 (2016).

    PubMed  Google Scholar 

  103. Pandit, L. et al. Relapsing optic neuritis and isolated transverse myelitis are the predominant clinical phenotypes for patients with antibodies to myelin oligodendrocyte glycoprotein in India. Mult. Scler. J. Exp. Transl Clin. https://doi.org/10.1177/2055217316675634 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Costa, B. K. D., Passos, G. R. D., Becker, J. & Sato, D. K. MOG-IgG associated optic neuritis is not multiple sclerosis. Arq. Neuropsiquiatr. 75, 687–691 (2017).

    PubMed  Google Scholar 

  105. Ogawa, R. et al. MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy. Neurol. Neuroimmunol. Neuroinflamm. 4, e322 (2017). The first description of the association of MOG-Abs with cortical encephalitis.

    PubMed  PubMed Central  Google Scholar 

  106. Hardy, T. A. et al. Atypical inflammatory demyelinating syndromes of the CNS. Lancet Neurol. 15, 967–981 (2016). An overview of atypical demyelinating disorders.

    CAS  PubMed  Google Scholar 

  107. Waters, P. et al. Multicentre comparison of a diagnostic assay: aquaporin-4 antibodies in neuromyelitis optica. J. Neurol. Neurosurg. Psychiatry 87, 1005–1015 (2016). A large, multicentre evaluation of assays for the detection of AQP4-Abs.

    PubMed  Google Scholar 

  108. Graus, F. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 15, 391–404 (2016).

    PubMed  PubMed Central  Google Scholar 

  109. Jarius, S. et al. MOG encephalomyelitis: international recommendations on diagnosis and antibody testing. J. Neuroinflamm. 15, 134 (2018).

    CAS  Google Scholar 

  110. Wells, E. et al. Neuroimmune disorders of the central nervous system in children in the molecular era. Nat. Rev. Neurol. 14, 433–445 (2018).

    PubMed  Google Scholar 

  111. Thompson, A. J., Baranzini, S. E., Geurts, J., Hemmer, B. & Ciccarelli, O. Multiple sclerosis. Lancet 391, 1622–1636 (2018).

    PubMed  Google Scholar 

  112. Wingerchuk, D. M. et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85, 177–189 (2015). Clinical criteria for autoimmune encephalitis.

    PubMed  PubMed Central  Google Scholar 

  113. Jurynczyk, M. et al. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain 140, 3128–3138 (2017). One of the largest studies of MOG-Abs.

    PubMed  Google Scholar 

  114. Cobo-Calvo, A. et al. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: the MOGADOR study. Neurology 90, e1858–e1869 (2018). One of the largest studies of MOG-Abs.

    CAS  PubMed  Google Scholar 

  115. Akaishi, T. et al. Different etiologies and prognoses of optic neuritis in demyelinating diseases. J. Neuroimmunol. 299, 152–157 (2016).

    CAS  PubMed  Google Scholar 

  116. Jarius, S. et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J. Neuroinflamm. 13, 280 (2016).

    Google Scholar 

  117. Jurynczyk, M. et al. Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis. Brain 140, 617–627 (2017).

    PubMed  Google Scholar 

  118. Sepulveda, M. et al. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes. J. Neurol. 263, 1349–1360 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Baumann, M. et al. MRI of the first event in pediatric acquired demyelinating syndromes with antibodies to myelin oligodendrocyte glycoprotein. J. Neurol. 265, 845–855 (2018).

    PubMed  Google Scholar 

  120. Hacohen, Y. et al. ‘Leukodystrophy-like’ phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease. Dev. Med. Child Neurol. 60, 417–423 (2018).

    PubMed  Google Scholar 

  121. Hacohen, Y. et al. Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease. JAMA Neurol. 75, 478–487 (2018).

    PubMed  PubMed Central  Google Scholar 

  122. Ramanathan, S. et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J. Neurol. Neurosurg. Psychiatry 89, 127–137 (2018).

    PubMed  Google Scholar 

  123. Biotti, D. et al. Optic neuritis in patients with anti-MOG antibodies spectrum disorder: MRI and clinical features from a large multicentric cohort in France. J. Neurol. 264, 2173–2175 (2017).

    PubMed  Google Scholar 

  124. Akaishi, T., Konno, M., Nakashima, I. & Aoki, M. Intractable hiccup in demyelinating disease with anti-myelin oligodendrocyte glycoprotein (MOG) antibody. Intern. Med. 55, 2905–2906 (2016).

    PubMed  PubMed Central  Google Scholar 

  125. Jarius, S. et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 3: brainstem involvement - frequency, presentation and outcome. J. Neuroinflamm. 13, 281 (2016).

    Google Scholar 

  126. Baumann, M. et al. Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): extending the spectrum of MOG antibody positive diseases. Mult. Scler. 22, 1821–1829 (2016).

    CAS  PubMed  Google Scholar 

  127. Huppke, P. et al. Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult. Scler. 19, 941–946 (2013).

    PubMed  Google Scholar 

  128. Wong, Y. Y. M. et al. Paediatric acute disseminated encephalomyelitis followed by optic neuritis: disease course, treatment response and outcome. Eur. J. Neurol. 25, 782–786 (2018).

    CAS  PubMed  Google Scholar 

  129. Fujimori, J. et al. Bilateral frontal cortex encephalitis and paraparesis in a patient with anti-MOG antibodies. J. Neurol. Neurosurg. Psychiatry 88, 534–536 (2017).

    PubMed  Google Scholar 

  130. Hamid, S. H. M. et al. Seizures and encephalitis in myelin oligodendrocyte glycoprotein IgG disease versus aquaporin 4 IgG disease. JAMA Neurol. 75, 65–71 (2018).

    PubMed  Google Scholar 

  131. Mariotto, S. et al. MOG antibody seropositivity in a patient with encephalitis: beyond the classical syndrome. BMC Neurol. 17, 190 (2017).

    PubMed  PubMed Central  Google Scholar 

  132. Havla, J. et al. Myelin-oligodendrocyte-glycoprotein (MOG) autoantibodies as potential markers of severe optic neuritis and subclinical retinal axonal degeneration. J. Neurol. 264, 139–151 (2017).

    CAS  PubMed  Google Scholar 

  133. Pache, F. et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients. J. Neuroinflamm. 13, 282 (2016).

    Google Scholar 

  134. Ramanathan, S. et al. Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis. Mult. Scler. 22, 470–482 (2016).

    CAS  PubMed  Google Scholar 

  135. Thompson, J. et al. The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 141, 348–356 (2018).

    PubMed  Google Scholar 

  136. Bradl, M., Reindl, M. & Lassmann, H. Mechanisms for lesion localization in neuromyelitis optica spectrum disorders. Curr. Opin. Neurol. 31, 325–333 (2018). An up-to-date review of the pathophysiology of NMOSD.

    PubMed  PubMed Central  Google Scholar 

  137. Lassmann, H., Brunner, C., Bradl, M. & Linington, C. Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions. Acta Neuropathol. 75, 566–576 (1988).

    CAS  PubMed  Google Scholar 

  138. Weissert, R. et al. MHC haplotype-dependent regulation of MOG-induced EAE in rats. J. Clin. Invest. 102, 1265–1273 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Weissert, R. et al. MHC class II-regulated central nervous system autoaggression and T cell responses in peripheral lymphoid tissues are dissociated in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. J. Immunol. 166, 7588–7599 (2001).

    CAS  PubMed  Google Scholar 

  140. Storch, M. K. et al. Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol. 8, 681–694 (1998).

    CAS  PubMed  Google Scholar 

  141. Lassmann, H. & Bradl, M. Multiple sclerosis: experimental models and reality. Acta Neuropathol. 133, 223–244 (2017).

    CAS  PubMed  Google Scholar 

  142. Bettelli, E., Baeten, D., Jager, A., Sobel, R. A. & Kuchroo, V. K. Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a Devic-like disease in mice. J. Clin. Invest. 116, 2393–2402 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Krishnamoorthy, G., Lassmann, H., Wekerle, H. & Holz, A. Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation. J. Clin. Invest. 116, 2385–2392 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Burrer, R. et al. Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies. Am. J. Pathol. 170, 557–566 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Peschl, P. et al. Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination. J. Neuroinflamm. 14, 208 (2017). A study that demonstrated that human MOG-Abs mediate demyelination ex vivo.

    Google Scholar 

  146. Saadoun, S. et al. Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol. Commun. 2, 35 (2014).

    PubMed  PubMed Central  Google Scholar 

  147. Flach, A. C. et al. Autoantibody-boosted T cell reactivation in the target organ triggers manifestation of autoimmune CNS disease. Proc. Natl Acad. Sci. USA 113, 3323–3328 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Mayer, M. C. et al. Distinction and temporal stability of conformational epitopes on myelin oligodendrocyte glycoprotein recognized by patients with different inflammatory central nervous system diseases. J. Immunol. 191, 3594–3604 (2013).

    CAS  PubMed  Google Scholar 

  149. Spadaro, M. et al. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Ann. Clin. Transl Neurol. 2, 295–301 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Kinzel, S. et al. Myelin-reactive antibodies initiate T cell-mediated CNS autoimmune disease by opsonization of endogenous antigen. Acta Neuropathol. 132, 43–58 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Spadaro, M. et al. Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Ann. Neurol. 84, 315–328 (2018). A study that demonstrated that human MOG-Abs mediate demyelination in vivo.

    CAS  PubMed  Google Scholar 

  152. Spadaro, M. et al. Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm 3, e257 (2016).

    PubMed  PubMed Central  Google Scholar 

  153. Hyun, J. W. et al. Evaluation of brain lesion distribution criteria at disease onset in differentiating MS from NMOSD and MOG-IgG-associated encephalomyelitis. Mult. Scler. https://doi.org/10.1177/1352458518761186 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  154. Jurynczyk, M. et al. Brain lesion distribution criteria distinguish MS from AQP4-antibody NMOSD and MOG-antibody disease. J. Neurol. Neurosurg. Psychiatry 88, 132–136 (2017).

    PubMed  Google Scholar 

  155. Geraldes, R. et al. The current role of MRI in differentiating multiple sclerosis from its imaging mimics. Nat. Rev. Neurol. 14, 199–213 (2018).

    PubMed  Google Scholar 

  156. Kortvelyessy, P. et al. ADEM-like presentation, anti-MOG antibodies, and MS pathology: TWO case reports. Neurol. Neuroimmunol. Neuroinflamm. 4, e335 (2017).

    PubMed  PubMed Central  Google Scholar 

  157. Konig, F. B. et al. Persistence of immunopathological and radiological traits in multiple sclerosis. Arch. Neurol. 65, 1527–1532 (2008).

    PubMed  Google Scholar 

  158. Di Pauli, F. et al. Fulminant demyelinating encephalomyelitis: insights from antibody studies and neuropathology. Neurol. Neuroimmunol. Neuroinflamm. 2, e175 (2015).

    PubMed  PubMed Central  Google Scholar 

  159. Wang, J. J. et al. Inflammatory demyelination without astrocyte loss in MOG antibody-positive NMOSD. Neurology 87, 229–231 (2016).

    PubMed  PubMed Central  Google Scholar 

  160. Lucchinetti, C. F., Bruck, W., Rodriguez, M. & Lassmann, H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol. 6, 259–274 (1996).

    CAS  PubMed  Google Scholar 

  161. Kaneko, K. et al. Myelin injury without astrocytopathy in neuroinflammatory disorders with MOG antibodies. J. Neurol. Neurosurg. Psychiatry 87, 1257–1259 (2016).

    PubMed  Google Scholar 

  162. Bennett, J. L. et al. Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann. Neurol. 66, 617–629 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Jarius, S. et al. Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance. J. Neuroinflamm. 7, 52 (2010).

    Google Scholar 

  164. Yanagida, A. et al. MOG-IgG-positive multifocal myelitis with intrathecal IgG synthesis as a spectrum associated with MOG autoimmunity: two case reports. J. Neurol. Sci. 382, 40–43 (2017).

    PubMed  Google Scholar 

  165. Papadopoulos, M. C., Bennett, J. L. & Verkman, A. S. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat. Rev. Neurol. 10, 493–506 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The research of M.R. is supported by research grants from the Austrian Federal Ministry of Science, Research and Education (grant BIG WIG MS, Markus Reindl), the Austrian Research promotion Agency (FFG, Bridge 1 project Nr. 853209 EDNA), the Austrian Science Funds (FWF, project W1206) and the Austrian Multiple Sclerosis Research Society. Research in the laboratory of P.W. is supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica, UK and the NIHR Oxford Biomedical Research Centre, UK.

Reviewer information

Nature Reviews Neurology thanks J. de Seze, M. Levy, S. Pittock and the other anonymous reviewers for their contribution to the peer review of this work.

Review criteria

We searched PubMed for original articles that were published between 1990 and 2018 and focused on anti-MOG antibodies in neurological diseases. We used the search terms “myelin oligodendrocyte glycoprotein”, “MOG”, “antibodies”, “autoantibodies”, “cell based assay”, “immunofluorescence”, “flow cytometry”, “multiple sclerosis”, “acute disseminated encephalomyelitis”, “neuromyelitis optica”, “optic neuritis” and “myelitis” alone and in combination. All articles identified were English-language, full-text papers. We also searched the reference lists of identified articles for further relevant papers. For the summaries of study results, only studies in which there were more than 10 patients per group were included.

Author information

Authors and Affiliations

  1. Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

    Markus Reindl

  2. Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK

    Patrick Waters

Authors
  1. Markus Reindl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Waters
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed equally to researching data for the article, discussion of the content, writing, and reviewing and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Markus Reindl.

Ethics declarations

Competing interests

The University Hospital and Medical University of Innsbruck (Austria; M.R.) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (Lübeck, Germany). P.W. is a named inventor on patents for antibody assays and has received royalties. He has received honoraria and/or consulting fees from Biogen, Euroimmun, Mereo Biopharma and Retrogenix, and has received travel grants from the Guthy-Jackson Charitable Foundation. He has received research funding from Euroimmun.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reindl, M., Waters, P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol 15, 89–102 (2019). https://doi.org/10.1038/s41582-018-0112-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41582-018-0112-x

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing