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Immunopathogenesis of multiple sclerosis

Published online by Cambridge University Press:  24 June 2014

Vesna Brinar*
Affiliation:
Department of Neurology, University hospital“Zagreb”, Croatia

Abstract:

Immunopathogenesis of multiple sclerosis is a complex process involving T cell mediated autoimmunity at initial stage of disease. A long standing view that Th1 cells are critical for early inflammatory development of lesions is challenging by recent findings that Th1 helper cells with Th17 phenotype are even more important. A complex autoimmunity of MS is further complicated with evidence that CD8 cells, regulatory T cells, clonal expansion of B cells, cells of myelin lineage, antibodies and complement, as well as process intrinsic to central nervous system contribute to the tissue destruction. Although there are a lot of evidences about inflammatory phase of MS, far less is known about mechanisms involved in degenerative phase of disease. It is not known weather quantitative, or qualitative differences in inflammatory response contributes to destruction of the tissue, or as it was shown experimentally demyelination may sometimes occur independent of T cells.

Understanding of immunopathogenesis of MS especially regarding various stages of disease is necessary for clinicians in choosing optimal therapy of MS in individual patients. Influences of immunomodulatory treatment on various stages of MS immuno-pathogenesis are presented.

Type
Main Theme: Multiple Sclerosis
Copyright
Copyright © 2009 John Wiley & Sons A/S

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References

References:

1.Martin, R, McFarland, HF, McFarlin, DE, Immunological aspects of demyelinating disorders. Ann Rev Immunol 1992:579621.Google Scholar
2.McFarland, H & Martin, R.Multiple sclerosis: a complicated picture of autoimmunity. Nature Immunology, 2007;9:913919.CrossRefGoogle Scholar
3.Lucchinetti, C, Bruck, W, Parisi, J, Scheithauer, B, Rodriguez, Z, Lassman, H.Heterogeneity of multiple sclerosis;implications for the pathogenesis of demyelination. Ann Neurol 2000;47;707–173.0.CO;2-Q>CrossRefGoogle ScholarPubMed
4.Zamvill, SS, Steinman, L.The T lymphocyte in experimental allergic encephalomyelitis. Ann Rev Immunol 1990:8:579621CrossRefGoogle Scholar
5.Matusevicius, D, Kivisakk, P, Navikas, V, Soderstrom, M, Fridrickson, S, Link, H.Interleukin 17-mRNA expression in blood and CSF mononuclear cells is augemented in multiple sclerosis. Mult Scler 1999;5:1001–104CrossRefGoogle Scholar
6.Brisebois, M, Zehntner, SP, Estrada, J, Owens, T, Fournier, S.A pathogenic role of CD8+ cells in spontaneous model of demyelinating disease. J Immunol 2006;177:24032411.CrossRefGoogle ScholarPubMed
7.Serafini, B, Rosicarelli, B, Franciotta, D, Magliozzi, R, Reynolds, R, Cinque, P, Andreoni, L, Trivedi, P, Salvetti, M, Faggioni, A, Aloisi, F.Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain. J Exp Med 2007;204:28992912CrossRefGoogle ScholarPubMed
8.Franciotta, D, Salvetti, M, Lolli, F, Serafini, B, Aloisi, F.B cells and multiple sclerosis. Lancet Neurology 2008;7:852–58CrossRefGoogle ScholarPubMed
9.Bailey, SL, Schreiner, B, McMahon, EJ.CNS myeloid DCs presenting endogenous myelin peptides preferentially polarize CD4+ Th17 cells in relapsing EAE. Nat Immunol 2007;8:172180.CrossRefGoogle ScholarPubMed
10.Allen, IV, McQuaid, S, Mirakhur, M, Nevin, G.Review: Pathological abnormalities in the normal appearing white matter in multiple sclerosis. Neurol Sci 2001;22:141144.CrossRefGoogle ScholarPubMed
11.Cepok, S, Zhou, D, Srivastava, R, Nessler, S, Stei, S, Büssow, K, Sommer, N, Hemmer, B.Identification of Epstein Barr virus protein as putative targets of the immune response in multiple sclerosis. J Clin Invest 2005;115:13521360.CrossRefGoogle ScholarPubMed
12.Genain, CP, Nguyen, MH, Letvin, NL, Pearl, R, Davis, RL, Adelman, M, Lees, MB, Linington, C, Hauser, SL.Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J Clin Invest 1995;96(6):29662974.CrossRefGoogle Scholar
13.Berger, T, Rubner, P, Schautzer, F, Egg, R, Ulmer, H, Mayringer, I, Dilitz, E, Deisenhammer, F, Reindl, M.Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 2003;349(2):139145.CrossRefGoogle ScholarPubMed
14.Zadro, I, Brinar, V, Horvat, G, Brinar, M.Clinical relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis. Clin Neurol Neurosurg 2007;109(1):2326. Epub 2006 06 5.CrossRefGoogle ScholarPubMed
15.Rebenko-Moll, NM, Lui, L, Cardona, A, Ransohoff, RM.Chemokines, mononuclear cells and nervous system: heaven (or hell) is in details. Curr Opin Immunol 2006;18: 683689.CrossRefGoogle ScholarPubMed
16.Pitt, D, Werner, P, Raine, CS.Glutamate excitoxicity in a model of multiple sclerosis. Nat Med 2000;6:6770.CrossRefGoogle Scholar
17.Barcellos, LF, Oksenberg, JR, Begovich, AB, Martin, ER, Schmidt, S, Vittinghoff, E, Goodin, DS, Pelletier, D, Lincoln, RR, Bucher, P, Swerdlin, A, Pericak-Vance, MA, Haines, JL, Hauser, SL.Multiple Sclerosis Genetics Group: HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. Am J Hum Genet 2003;72: 710766.CrossRefGoogle ScholarPubMed
18.Pete, M, Fujuta, K, Kitze, B, Whitaker, JN, Albert, Eet al.Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. Neurology 1990;45:540548.Google Scholar
19.Sakaguchi, S.Natural arising CD4+ regulatory T cell immunologic self tolerance, and negative control of immune responses. Ann Rev Immunol 2004;22:531562.CrossRefGoogle ScholarPubMed
20.Hafler, D, Slavik, JM, Anderson, DE, O'Connor, KC, De Jager, P, Baecher-Allan, C.Multiple Sclerosis Immunological Reiews 2005;208231.Google Scholar
21.Stüve, O, Dooley, NP, Uhm, JH, Antel, JP, Francis, GS, Williams, G, Yong, VW.Interferon beta 1b decrease the migration of T lymphocytes in vivo: effects on matrix metalloproteinase-9. Ann Neurol 1996;40:853863.CrossRefGoogle Scholar
22.Kappos, L, Bates, D, Hartung, HP, Havrdova, E, Miller, D, Polman, CH, Ravnborg, M, Hauser, SL, Rudick, RA, Weiner, HL, O'Connor, PW, King, J, Radue, EW, Yousry, T, Major, EO, Clifford, DB.Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol 2007;6(6):431441.CrossRefGoogle ScholarPubMed
23.O'Connor, P, Comi, G, Montalban, X, Antel, J, Radue, EW, de Vera, A, Pohlmann, H, Kappos, L.FTY720 D2201 Study Group:Oral fingolimod (FTY720) in multiple sclerosis: two-year results a phase II extension study. Neurology 2009:72(1):7379.CrossRefGoogle Scholar
24.Coles, AJ, Compston, AD. Monoclonal antibody treatment exposes three mechanisms underlying clinical course of multiple sclerosis. Ann Neurol 1999;46:296304.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
25.Hauser, SL, Waubant, E, Arnold, DL, Vollmer, T, Antel, J, Fox, RJ, Bar-Or, A, Panzara, M, Sarkar, N, Agarwal, S, Langer-Gould, A, Smith, CH. HERMES Trial Group:B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008;358(7):676688.CrossRefGoogle Scholar
26.Bielekova, B, Howard, T, Packer, AN, Richert, N, Blevins, G, Ohayon, J, Waldmann, TA, McFarland, HF, Martin, R.Effect of anti CD25 antibody daclizumab in the inhibition of inflammation and stabilization of disease progression in multiple sclerosis. Arch Neurol 2009;66(4):493499.CrossRefGoogle Scholar