AntiMOG associated encephalomyelitis

AntiMOG associated encephalomyelitis is an inflammatory demyelinating disease previously considered part of the multiple sclerosis spectrum, and currently considered an independent disease.[1]

Antibodies against the Myelin oligodendrocyte glycoprotein have received much of its laboratory attention in studies dealing with multiple sclerosis (MS). Several studies had pointed to a role for antibodies against MOG in the pathogenesis of MS, but most of them were written before the discovery of NMO-IgG and the NMO spectrum of diseases. MOG antibodies are currently considered mostly absent in multiple sclerosis.[2]

Though some patients present brain lesions they do not have the ovoid shape perpendicular to the ventricle typical of MS.[3]

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.[4]

Conditions related to anti-MOG

The presence of anti-MOG autoantibodies has been associated with the following conditions[5]

Some of them have been studied in detail:

Seronegative neuromyelitis optica

Anti-MOG autoimmunity has been found to be involved in the seronegative NMO[14][15] and also in optic neuritis and some fulminant forms of ADEM[8] MOG antibodies in NMOSD are variable depending on the seropositivity status[16]

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[17]

Double positive NMO

Some NMO patients present double positive for autoantibodies to AQP4 and MOG. These patients have MS-like brain lesions, multifocal spine lesions and retinal and optic nerves atrophy.[18]

Histopathology

Demyelinating lesions of AntiMOG associated encephalomyelitis resemble MS pattern-II lesions.[19] The demyelinating lesion presents T-cells and macrophages around blood vessels, with preservation of oligodendrocytes and signs of complement system activation.

Treatment

The anti-MOG spectrum has been found to be responsive to steroids,[20] and also to plasmapheresis, as any other pattern-II Inflammatory demyelinating diseases of the central nervous system.[21][22]

Anti-MOG positive patients should not be treated with interferons. It has been reported to make the disease worse.[4] There are also anecdotal reports against using Fingolimod.[23]

Causes

The causes why anti-MOG antibodies appear in the serum are still not known, but a connection to infectious mononucleosis has been proposed[24]

History

Reports about the involvement of anti-MOG antibodies in MS and other demyelinating diseases were appearing since the late 1980s, but evidence was always weak and inconsistent.

The turning point, was in 2011, when Mader et al. developed a CBA assay using HEK 293 cells and observed that it had a higher specificity to detect anti-MOG in serum. These authors reported that some patients with NMOSD had high titers of anti-MOG antibodies similar to ADEM.[25]

Since that moment, anti-MOG seropositivity has been found consistently in ADEM, NMO, pediatric MS and atypical MS.

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[26] 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,[26] and currently it is considered even a biomarker against the MS diagnosis[27][28]

References

  1. ↑ Sudarshini Ramanathan, Russell C. Dale, Fabienne Brilot, Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmunity Reviews, Volume 15, Issue 4, April 2016, Pages 307–324, doi:10.1016/j.autrev.2015.12.004
  2. ↑ Ketelslegers, I. A.; Van Pelt, D. E.; Bryde, S.; Neuteboom, R. F.; Catsman-Berrevoets, C. E.; Hamann, D.; Hintzen, R. Q. (6 February 2015). "Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort". Multiple Sclerosis Journal. 21 (12): 1513–1520. doi:10.1177/1352458514566666. PMID 25662345.
  3. ↑ Kim, Sung-Min; et al. (2015). "Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS". Neurol Neuroimmunol Neuroinflamm. 2 (6): e163. doi:10.1212/NXI.0000000000000163.
  4. 1 2 Nakashima, Ichiro. "Anti-myelin oligodendrocyte glycoprotein antibody in demyelinating diseases". Clinical and Experimental Neuroimmunology. 6: 59–63. doi:10.1111/cen3.12262.
  5. 1 2 3 Reindl, M; Di Pauli, F; Rostásy, K; Berger, T (Aug 2013). "The spectrum of MOG autoantibody-associated demyelinating diseases". Nat Rev Neurol. 9 (8): 455–61. doi:10.1038/nrneurol.2013.118. PMID 23797245.
  6. ↑ Spadaro, Melania; et al. "Histopathology and clinical course of MOG-antibody-associated encephalomyelitis". Annals of Clinical and Translational Neurology. 2 (3): 295–301. doi:10.1002/acn3.164.
  7. ↑ Baumann, M.; Hennes, E.M.; Schanda, K.; Karenfort, M.; Bajer-Kornek, B.; Diepold, K.; Fiedler, B.; Marquardt, I.; Strautmanis, J.; Vieker, S.; Reindl, M.; Rostásy, K. (2015). "Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies". European Journal of Paediatric Neurology. 19 (Supplement 1): S21. doi:10.1016/S1090-3798(15)30066-0.
  8. 1 2 Di Pauli, Franziska; et al. (2015). "Fulminant demyelinating encephalomyelitis". Neurol Neuroimmunol Neuroinflamm. 2 (6): e175. doi:10.1212/NXI.0000000000000175.
  9. ↑ 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;
  10. ↑ Franziska Di Pauli, Romana Höftberger, Markus Reindl, Ronny Beer, Paul Rhomberg, Kathrin Schanda, Douglas Sato, Kazuo Fujihara, Hans Lassmann, Erich Schmutzhard and Thomas Berger, Fulminant demyelinating encephalomyelitis. Insights from antibody studies and neuropathology. Neurol Neuroimmunol Neuroinflamm December 2015 vol. 2 no. 6 e175. doi=http://dx.doi.org/10.1212/NXI.0000000000000175
  11. ↑ Melania Spadaro et al., Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis, Neurol Neuroimmunol Neuroinflamm, October 2016 vol. 3 no. 5 e257, doi: http://dx.doi.org/10.1212/NXI.0000000000000257
  12. ↑ Chalmoukou, Konstantina; et al. (2015). "Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis". Neurol Neuroimmunol Neuroinflamm. 2 (4): e131. doi:10.1212/NXI.0000000000000131.
  13. ↑ Konstantina Chalmoukou et al. Recurrent Optic Neuritis (rON) is characterised by Anti-MOG Antibodies: A follow-up study" Neurology 2015; vol. 84 no. 14 Supplement P5.274
  14. ↑ Pröbstel, Anne-Katrin; et al. (2015). "Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype". Journal of Neuroinflammation. 12 (1): 46. doi:10.1186/s12974-015-0256-1.
  15. ↑ CYNTHIA MCKELVEY, Press Report, What’s the Role of Myelin Oligodendrocyte Glycoprotein in NMO?
  16. ↑ Berger, T.; Reindl, M. (2015). "Antibody biomarkers in CNS demyelinating diseases – a long and winding road,". European Journal of Neurology. 22 (8): 1162–1168. doi:10.1111/ene.12759.
  17. ↑ 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
  18. ↑ Ya, Yaping; et al. (2015). "Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD". Science China Life Sciences. doi:10.1007/s11427-015-4997-y.
  19. ↑ 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.
  20. ↑ Ichiro Nakashima, Anti-myelin oligodendrocyte glycoprotein antibody in demyelinating diseases, December 2015, DOI: 10.1111/cen3.12262
  21. ↑ Oshiro A, Nakamura S, Tamashiro K, Fujihara K. Anti-MOG + neuromyelitis optica spectrum disorders treated with plasmapheresis, No To Hattatsu. 2016 May;48(3):199-203
  22. ↑ Rocio Vazquez do Campo, Ramon Yarza, Sebastian Lopez Chiriboga and Kevin Barrett, Myelin Oligodendrocyte Glycoprotein (MOG) Autoimmunity. A Case Report, Neurology April 5, 2016 vol. 86 no. 16 Supplement P5.346
  23. ↑ Miyazaki T, Nakajima H, Motomura M, Tanaka K, Maeda Y, Shiraishi H, Tsujino A., A case of recurrent optic neuritis associated with cerebral and spinal cord lesions and autoantibodies against myelin oligodendrocyte glycoprotein relapsed after fingolimod therapy. Rinsho Shinkeigaku. 2016 Apr 28;56(4):265-9. doi: 10.5692/clinicalneurol.cn-000756. Epub 2016 Mar 24. PMID 27010093
  24. ↑ Kakalacheva, Kristina; et al. (2016). "Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein". Viruses. 8 (2): 51. doi:10.3390/v8020051.
  25. ↑ Mader S, Gredler V, Schanda K, et al. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflammation. 2011; 8: 184.
  26. 1 2 Kezuka; et al. (2012). "Relationship Between NMO-Antibody and Anti–MOG Antibody in Optic Neuritis". Journal of Neuro-Ophthalmology. 32 (2): 107–110. doi:10.1097/WNO.0b013e31823c9b6c.
  27. ↑ Ketelslegers, Immy A; Van Pelt, Daniëlle E; Bryde, Susanne; Neuteboom, Rinze F; Catsman-Berrevoets, Coriene E; Hamann, Dörte; Hintzen, Rogier Q. "Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort". Mult Scler. 21: 1513–1520. doi:10.1177/1352458514566666.
  28. ↑ Kitley, Joanna; et al. (2012). "Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype". Neurology. 79 (12): 1273–1277. doi:10.1212/WNL.0b013e31826aac4e.
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