AntiMOG associated encephalomyelitis

Antibodies against the Myelin oligodendrocyte glycoprotein have received much of its laboratory attention in studies dealing with multiple sclerosis (MS). Several studies have shown a role for antibodies against MOG in the pathogenesis of MS.[1] though most of them were written before the discovery of NMO-IgG and the NMO spectrum of diseases.

Though some patients present brain lesions they do not have the ovoid shape perpendicular to the ventricle typical of MS[2].

Anti-MOG status is different depending whether it is measured by ELISA or by microarray (CBA). The proper way to identify it is by microarray, reacting patient serum with living cells, and detecting the binding IgG via a fluorescent-labeled secondary antibody.[3]

Conditions related to anti-MOG

The presence of anti-MOG autoantibodies has been associated with the following conditions[4]

Some of them have been studied in detail:

Seronegative neuromyelitis optica

Anti-MOG autoimmunity has been found to be involved in the seronegative NMO[10][11] and also in optic neuritis and some fulminant forms of ADEM[7] MOG antibodies in NMOSD are variable depending on the seropositivity status[12]

Pediatric demyelination

The anti-MOG spectrum in children is equally variated: Out of a sample of 41 children with MOG-antibodies 29 had clinical NMOSD (17 relapsing), 8 had ADEM (4 relapsing with ADEM-ON), 3 had a single clinical event CIS, and 1 had a relapsing tumefactive disorder. Longitudinal myelitis was evident on MRI in 76[percent]. It has also been noted that percentage of children with anti-mog antibodies respect a demyelinating sample is higher than for adults[13]

Histopathology

Demyelinating lesions of AntiMOG associated encephalomyelitis resemble MS pattern-II lesions.[14] The demyelinating lesion presents T-cells and macrophages around blood vessels, with preservation of oligodendrocytes and signs of complement system activation.

Causes

The causes why anti-MOG antibodies appear in the serum are still not known, but a connection to infectious mononucleosis has been proposed[15]

Animal models

Animal models of MS, EAE, have shown that “MOG-specific EAE models (of different animal strains) display/mirror human multiple sclerosis" but basically explains the part involved in the optic neuritis[16] These models with anti-MOG antibodies have been investigated extensively and are considered the only antibodies with demyelinating capacity but again, EAE pathology is closer to NMO and ADEM than to the confluent demyelination observed in MS.

Anti-MOG mediated demyelination was shown to behave similar to NMO in animal models,[16] and currently it is considered even a biomarker against the MS diagnosis[17][18]

References

  1. ↑ Berger T, Rubner P, Schautzer F, Egg R, Ulmer H, Mayringer I, Dilitz E, Deisenhammer F, Reindl M (July 2003). "Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event". N. Engl. J. Med. 349 (2): 139–45. doi:10.1056/NEJMoa022328. PMID 12853586.
  2. ↑ Sung-Min Kim et al. Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS. Neurol Neuroimmunol Neuroinflamm December 2015 vol. 2 no. 6 e163. Published online October 15, 2015 doi: http:/​/​dx.​doi.​org/​10.​1212/​NXI.​0000000000000163
  3. ↑ Ichiro Nakashima, Anti-myelin oligodendrocyte glycoprotein antibody in demyelinating diseases
  4. 1 2 3 Reindl M, Di Pauli F, Rostásy K, Berger T. The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol. 2013 Aug;9(8):455-61. doi: 10.1038/nrneurol.2013.118. Epub 2013 Jun 25. PMID 23797245
  5. ↑ Melania Spadaro et al. Histopathology and clinical course of MOG-antibody-associated encephalomyelitis. Annals of Clinical and Translational Neurology Volume 2, Issue 3, pages 295–301, March 2015. DOI: 10.1002/acn3.164
  6. ↑ M. Baumann, E.M. Hennes, K. Schanda, M. Karenfort, B. Bajer-Kornek, K. Diepold, B. Fiedler, I. Marquardt, J. Strautmanis, S. Vieker, M. Reindl, K. Rostásy. Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies. European Journal of Paediatric Neurology, Volume 19, Supplement 1, May 2015, Pages S21, Abstracts of the 11th EPNS Congress. 22 May 2015. doi:10.1016/S1090-3798(15)30066-0
  7. 1 2 Franziska Di Pauli et al. Fulminant demyelinating encephalomyelitis, Neurol Neuroimmunol Neuroinflamm December 2015 vol. 2 no. 6 e175, doi: http://dx.doi.org/10.1212/NXI.0000000000000175
  8. ↑ Jarius S, Metz I, König FB, Ruprecht K, Reindl M, Paul F, Brück W, Wildemann B.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. 2016 Feb 11. pii: 1352458515622986.
  9. ↑ Konstantina Chalmoukou et al. Recurrent Optic Neuritis (rON) is characterised by Anti-MOG Antibodies: A follow-up study. Neurology April 6, 2015 vol. 84 no. 14 Supplement P5.274
  10. ↑ Anne-Katrin Pröbstel et al. Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype. Journal of Neuroinflammation Volume 12, 2015, 12:46 doi:10.1186/s12974-015-0256-1
  11. ↑ CYNTHIA MCKELVEY, Press Report, What’s the Role of Myelin Oligodendrocyte Glycoprotein in NMO?
  12. ↑ T. Berger, M. Reindl, Antibody biomarkers in CNS demyelinating diseases – a long and winding road, DOI: 10.1111/ene.12759, European Journal of Neurology, Volume 22, Issue 8, pages 1162–1168, August 2015
  13. ↑ Silvia Tenembaum et al. Spectrum of MOG Autoantibody-Associated Inflammatory Diseases in Pediatric Patients, Neurology April 6, 2015 vol. 84 no. 14 Supplement I4-3A
  14. ↑ Spadaro Melania; et al. (2015). "Histopathology and clinical course of MOG-antibody-associated encephalomyelitis". Annals of Clinical and Translational Neurology 2 (3): 295–301. doi:10.1002/acn3.164.
  15. ↑ Kristina Kakalacheva et al. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein. Viruses 2016, 8(2), 51; doi:10.3390/v8020051
  16. 1 2 Kezuka et al. Relationship Between NMO-Antibody and Anti–MOG Antibody in Optic Neuritis. Journal of Neuro-Ophthalmology: June 2012 - Volume 32 - Issue 2 - p 107–110 doi: 10.1097/WNO.0b013e31823c9b6c
  17. ↑ Immy A Ketelslegers, Daniëlle E Van Pelt, Susanne Bryde, Rinze F Neuteboom, Coriene E Catsman-Berrevoets, Dörte Hamann, and Rogier Q Hintzen Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort Mult Scler 1352458514566666, first published on February 6, 2015 doi:10.1177/1352458514566666
  18. ↑ Joanna Kitley, et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology September 18, 2012 vol. 79 no. 12 1273-1277. doi: 10.1212/WNL.0b013e31826aac4e
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