Autoantibodies against myelin antigens in patients with neuromyelitis optica

Kota Moriguchi, Katsuichi Miyamoto, Juri Ichihashi, Susumu Kusunoki

Department of Internal Medicine 3, National Defense Medical College, Tokorozawa, Japan.
Department of Neurology, Kinki University School of Medicine, Osaka, Japan.

DOI: 10.4236/oji.2013.32007                

Abstract

In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO); titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.

Keywords

Neuromyelitis Optica; Anti-Myelin Antibody; Myelin Oligodendrocyte Glycoprotein; Proteolipid Protein; Myelin Basic Protein

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Wingerchuk, D.M. and Weinshenker, B.G. (2003) Neuromyelitis optica: Clinical predictors of a relapsing course and survival. Neurology, 60, 848-853. doi:10.1212/01.WNL.0000049912.02954.2C
[2]	Carroll, W.M. and Fujihara, K. (2010) Neuromyelitis optica. Current Treatment Options in Neurology, 12, 244-255. doi:10.1007/s11940-010-0071-z
[3]	Marignier, R., Nicolle, A., Watrin, C., et al. (2010) Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury. Brain, 133, 2578-2591. doi:10.1093/brain/awq177
[4]	Sospedra, M. and Martin, R. (2005) Immunology of multiple sclerosis. Annual Reviews of Immunology, 23, 683-747.doi:10.1146/annurev.immunol.23.021704.115707
[5]	Kerlero de Rosbo, N., Honegger, P., Lassmann, H., et al. (1990) Demyelination induced in aggregating brain cell cultures by a monoclonal antibody against myelin/oligodendrocyte glycoprotein. Journal of Neurochemistry, 55, 583-587. doi:10.1111/j.1471-4159.1990.tb04173.x
[6]	Stefferl, A., Brehm, U., Storch, M., et al. (1999) Myelin oligodendrocyte glycoprotein induces experimental autoimmune encephalomyelitis in the resistant. Journal of Immunology, 163, 40-49.
[7]	Pittock, S.J., Reindl, M., Achenbach, S., et al. (2007) Myelin oligodendrocyte glycoprotein antibodies in pathologically proven multiple sclerosis: Frequency, stability and clinicopathologic correlations. Multiple Sclerosis Journal, 13, 7-16. doi:10.1177/1352458506072189
[8]	Wang, H., Munger, K.L., Reindl, M., et al. (2008) Myelin oligodendrocyte glycoprotein antibodies and multiple sclerosis in healthy young adults. Neurology, 71, 1142-1146.
[9]	Kezuka, T., Usui, Y., Yamakawa, N., et al. (2012) Relationship between NMO-antibody and anti-MOG antibody in optic neuritis. Journal of Neuro-Ophthalmology, 32, 107-110. doi:10.1097/WNO.0b013e31823c9b6c
[10]	Wingerchuk, D.M., Lennon, V.A., Pittock, S.J., et al. (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology, 66, 1485-1489. doi:10.1212/01.wnl.0000216139.44259.74
[11]	Johns T.G. and Bernard C.C. (1999) The structure and function of myelin oligodendrocyte glycolprotein. Journal of Neurochemistry, 72, 1-9. doi:10.1111/j.1471-4159.1999.tb11579.x
[12]	Khalis, M., Reindl, M., Lutterotti, A., et al. (2006) Epitope specificity of serum antibodies directed against the extracellular domain of myelin oligodendrocyte glycolprotein: Influence of relapses and immunomodulatory treatments. Journal of Neuroimmunology, 174, 147-156.
[13]	Berger, T., Rubner, P., Schautzer, F., et al. (2003) Anti-myelin antibodies as a predictor of clinically definitive multiple sclerosis after a first demyelinating event. The New England Journal of Medicine, 349, 139-145. doi:10.1056/NEJMoa022328
[14]	Tomassini, V., De Giglio, L., Reindl, M., et al. (2007) Anti-myelin antibodies predict the clinical outcome after a first episode suggestive of MS. Multiple Sclerosis Journal, 13, 1086-1094. doi:10.1177/1352458507077622
[15]	Rauer, S., Euler, B., Reindl, M. and Berger, T. (2006) Antimyelin antibodies and the risk of relapse in patients with a primary demyelinating event. Journal of Neurology, Neurosurgery & Psychiatry, 77, 739-742. doi:10.1136/jnnp.2005.077784
[16]	Kuhle, J., Pohl, C., Mehling, M., et al. (2007) Lack of association between antimyelin antibodies and progresssion to multiple sclerosis. The New England Journal of Medicine, 356, 371-378. doi:10.1056/NEJMoa063602
[17]	Lim, E.T., Berger, T., Reindl, M., et al. (2005) Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis. Multiple Sclerosis, 11, 492-494.
[18]	Pelayo, R., Tintoré, M., Montalban, X., et al. (2007) Anti-myelin antibodies with no progression to multiple sclerosis. The New England Journal of Medicine, 356, 426-428. doi:10.1056/NEJMc062467
[19]	Haase, C.G. and Schmidt, S. (2001) Detection of brain-specific autoantibodies to myelin oligodendrocyte glycolprotein, S100β and myelin basic protein in patients with Devic’s neuromyelitis optica. Neuroscience Letters, 307, 131-133. doi:10.1016/S0304-3940(01)01949-8
[20]	Correale, J. and Fiol, M. (2004) Activation of humoral immunity and eosinophils in neuromyelitis optica. Neurology, 63, 2363-2370. doi:10.1212/01.WNL.0000148481.80152.BF
[21]	Alves-Leon, S.V., Pimentel, M.L., Sant’Anna, G., et al. (2008) Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica. Arquivos de Neuro-Psiquiatr, 66, 678-684. doi:10.1590/S0004-282X2008000500013
[22]	Kahlenberg, J.M. (2011) Neuromyelitis optica spectrum disorder as an initial presentation of primary Sjögren’s syndrome. Seminars in Arthritis and Rheumatism, 40, 343-348. doi:10.1016/j.semarthrit.2010.05.005
[23]	Pittock, S.J., Lennon, V.A., De Seze, J., et al. (2008) Neuromyelitis optica and non-organ-specific autoimmunity. Archives of Neurology, 65, 78-83. doi:10.1001/archneurol.2007.17
[24]	Takano, R., Misu, T., Takahashi, T., et al. (2010) Astrocytic damage is far more severe than demyelination in NMO. Neurology, 75, 208-216. doi:10.1212/WNL.0b013e3181e2414b
[25]	Marignier, R., Giraudon, P., Vukusic, S., et al. (2010) Anti-aquaporin-4 antibodies in Devic’s neuromyelitis optica: Therapeutic implications. Therapeutic Advances in Neurological Disorders, 3, 311-321. doi:10.1177/1756285610382478