Advertisement

Immunopathogenic and clinical relevance of antibodies against myelin oligodendrocyte glycoprotein (MOG) in Multiple Sclerosis

  • T Berger
  • M Reindl
Conference paper

Summary

Recent neuropathological findings identified four distinct immunopathogenic pathways of demyelination and tissue destruction in the most common inflammatory demyelinating central nervous system disorder, Multiple Sclerosis. One of this neuropathological subtypes is characterised by features of antibody-mediated demyelination. A role of anti-myelin antibodies in the disease evolution of multiple sclerosis has been suggested already for a long time, however, their pathogenetic and clinical relevance is not understood yet. This present article will discuss recently published and some preliminary data on the immunopathogenic role of antibodies against myelin oligodendrocyte glycoprotein (MOG) and other myelin/nonmyelin targets in multiple sclerosis, as well as possible clinical implications for prognosis and therapy in the future.

Keywords

Multiple Sclerosis Multiple Sclerosis Patient Myelin Basic Protein Major Histocompatibility Complex Locus Major Histocompatibility Complex Haplotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adelmann M, Wood J, Benzel I, Fiori P, Lassmann H, Matthieu JM, Gardinier MV, Dornmair K, Linington C (1995) The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat. J Neuroimmunol 63: 17–27PubMedCrossRefGoogle Scholar
  2. Amadou C, Ribouchon MT, Mattei MG, Jenkins NA, Gilbert DJ, Copeland NG, Avoustin P, Pontarotti P (1995) Localization of new genes and markers to the distal part of the human major histocompatibility complex (MHC) region and comparison with the mouse: new insights into the evolution of mammalian genomes. Genomics 26: 9–20PubMedCrossRefGoogle Scholar
  3. Amor S, Groome N, Linington C, Morris MM, Dornmairm K, Gardinier MV, Matthieu JM, Baker D (1994) Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice. J Immunol 153: 4349–4356PubMedGoogle Scholar
  4. Baig S, Olsson T, Yu-Ping J, Hojeberg B, Cruz M, Link H (1991) Multiple Sclerosis: cells secreting antibodies against myelin-associated glycoprotein are present in cerebrospinal fluid. Scand J Immunol 33: 73–79PubMedCrossRefGoogle Scholar
  5. Bruck W, Schmied M, Suchanek G, Bruck Y, Breitschopf H, Poser S, Piddlesden S, Lassmann H (1994) Oligodendrocytes in the early course of Multiple Sclerosis. Ann Neurol 35: 65–73PubMedCrossRefGoogle Scholar
  6. Brunner C, Lassmann H, Waehneldt TV, Matthieu JM, Linington C (1989) Differential ultrastructural localization of myelin basic protein, myelin/o1igodendroglial glycoprotein, and 2’,3’-cyclic nucleotide 3’-phosphodiesterase in the CNS of adult rats. J Neurochem 52: 296–304PubMedCrossRefGoogle Scholar
  7. Charcot JM (1868) Histologie de la sclerosis en plaque. Gaz Hopital (Paris) 42: 554Google Scholar
  8. Chataway J, Feakes R, Coraddu F, Gray J, Deans J, Fraser M, Robertson N, Broadley S, Jones H, Clayton D, Goodfellow P, Sawcer S, Compston A (1998) The genetics of Multiple Sclerosis: principles, background and updated results of the United Kingdom systematic genome screen. Brain 121: 1869–1887PubMedCrossRefGoogle Scholar
  9. Couratier P, Yi FH, Preud’homme JL, Clavelou P, White A, Sindou P, Vallat JM, Jauberteau MO (1998) Serum autoantibodies to neurofilament proteins in sporadic amyotrophic lateral sclerosis. J Neurol Sci 154: 137–145PubMedCrossRefGoogle Scholar
  10. Gardinier MV, Amiguet P, Linington C, Matthieu JM (1992) Myelin/oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily. J Neurosci Res 33: 177–187PubMedCrossRefGoogle Scholar
  11. Gay D, Esiri M (1991) Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytological study. Brain 114: 557–572PubMedCrossRefGoogle Scholar
  12. Genain CP, Nguyen MH, Letvin NL, Pearl R, Davis RL, Adelman M, Lees MB, Linington C, Hauser SL (1995) Antibody facilitation of Multiple Sclerosis-like lesions in a nonhuman primate. J Clin Invest 96: 2966–2974PubMedCrossRefGoogle Scholar
  13. Genain CP, Cannella B, Hauser SL, Raine CS (1999) Identification of autoantibodiesassociated with myelin damage in Multiple Sclerosis. Nat Med 5: 170–175PubMedCrossRefGoogle Scholar
  14. Giovannoni G, Hartung HP (1996) The immunopathogenesis of Multiple Sclerosis andGuillain-Barre syndrome. Curr Opin Neurol 9: 165–177PubMedCrossRefGoogle Scholar
  15. Hilton AA, Slavin AJ, Hilton DJ, Bernard CC (1995) Characterization of cDNA and genomic clones encoding human myelin oligodendrocyte glycoprotein. J Neurochem 65: 309–318PubMedCrossRefGoogle Scholar
  16. Jacobs LD, Cookfair DL, Rudick RA, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Grange CV, Simon JH, Alam JJ, Bartoszak DM, Bourdette DN, Braiman J, Brownscheidle CM, Coats ME, Cohan SL, Dougherty DS, Kinkel RP, Mass MK, Munschauer FE, Priore RL, Pullicino PM, Scherokman BJ, Whitham RH (1996) Intramuscular interferon beta-la for disease progression in relapsing Multiple Sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 39: 285–294PubMedCrossRefGoogle Scholar
  17. Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB (1995) Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 45: 1268–1276PubMedCrossRefGoogle Scholar
  18. Kerlero de Rosbo N, Honegger P, Lassmann H, Matthieu JM (1990) Demyelination induced in aggregating brain cell cultures by a monoclonal antibody against myelin/ oligodendrocyte glycoprotein. J Neurochem 55: 583–587PubMedCrossRefGoogle Scholar
  19. Kerlero de Rosbo N, Milo R, Lees MB, Burger D, Bernard CC, Ben-Nun A (1993) Reactivity to myelin antigens in Multiple Sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein. J Clin Invest 92: 2602–2608PubMedCrossRefGoogle Scholar
  20. Kroepfl JF, ViisE LR, CharroN AJ, Linington C, Gardinier MV (1996) Investigation of myelin/oligodendrocyte glycoprotein membrane topology. J Neurochem 67: 2219–2222PubMedCrossRefGoogle Scholar
  21. Lassmann H, Raine CS, AnteL J, Prineas JW (1998) Immunopathology of Multiple Sclerosis: report on an international meeting held at the Institute of Neurology of the University of Vienna. J Neuroimmunol 86: 213–217PubMedCrossRefGoogle Scholar
  22. Lebar R, Lubetzki C, Vincent C, Lombrail P, Boutry JM (1986) The M2 autoantigen of central nervous system myelin, a glycoprotein present in oligodendrocyte membrane. Clin Exp Immunol 66: 423–434PubMedGoogle Scholar
  23. Lehmann PV, Forsthuber T, Miller A, SercarZ EE (1992) Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 358: 155–157PubMedCrossRefGoogle Scholar
  24. Linington C, Lassmann H (1987) Antibody responses in chronic relapsing experimental allergic encephalomyelitis: correlation of serum demyelinating activity with antibody titre to the myelin/oligodendrocyte glycoprotein (MOG). J Neuroimmunol 17: 61–69PubMedCrossRefGoogle Scholar
  25. Linington C, Bradl M, Lassmann H, Brunner C, Vass K (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 130: 443–454PubMedGoogle Scholar
  26. Lucchinetti CF, Bruck W, Rodriguez M, Lassmann H (1996) Distinct patterns of Multiple Sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol 6: 259–274PubMedCrossRefGoogle Scholar
  27. Malfroy L, Viratelle C, Coppin H, Borot N, Roth MP (1995) Polymorphic tri-and tetranucleotide repeats in exons 1 and 8 of the myelin oligodendrocyte glycoprotein (MOG) gene. Hum Genet 96: 737–738PubMedCrossRefGoogle Scholar
  28. Martin R, McFarland HF (1995) Immunological aspects of experimental allergic encephalomyelitis and Multiple Sclerosis. Crit Rev Clin Lab Sci 32: 121–182PubMedCrossRefGoogle Scholar
  29. Mithen F, Bunge R, Agrawal H (1980) Proteolipid protein antiserum does not affect CNSPubMedCrossRefGoogle Scholar
  30. myelin in rat spinal cord culture. Brain Res 197: 477–483PubMedCrossRefGoogle Scholar
  31. Mithen FA, Agrawal HC, Eylar EH, Fishman MA, Blank W, Bunge RP (1982a) Studies with antisera against peripheral nervous system myelin and myelin basic proteins. I. Effects of antiserum upon living cultures of nervous tissue. Brain Res 250: 321–331PubMedCrossRefGoogle Scholar
  32. Mithen FA, Agrawa, HC, Fishman MA, Eylar EH, Bunge RP (1982b) Studies with antisera against peripheral nervous system myelin and myelin basic proteins. II. Immunohistochemical studies in cultures of rat dorsal root ganglion neurons and Schwann cells. Brain Res 250: 333–343PubMedCrossRefGoogle Scholar
  33. Moller JR, Johnson D, Brady RO, Tourtellotte WW, Quarles RH (1989) Antibodies to myelin-associated glycoprotein (MAG) in the cerebrospinal fluid of Multiple Sclerosis patients. J Neuroimmunol 22: 55–61PubMedCrossRefGoogle Scholar
  34. Newcombe J, Gahan S, Cuzner ML (1985) Serum antibodies against central nervous system proteins in human demyelinating disease. Clin Exp Immunol 59: 383–390PubMedGoogle Scholar
  35. Olsson T, Baig S, Hojeberg B, Link H (1990) Antimyelin basic protein and antimyelin antibody-producing cells in Multiple Sclerosis. Ann Neurol 27: 132–136PubMedCrossRefGoogle Scholar
  36. Ozawa K, Suchanek G, Breitschopf H, Bruck W, Budka H, Jellinger K, Lassmann H (1994) Patterns of oligodendroglia pathology in Multiple Sclerosis. Brain 117: 1311–1322PubMedCrossRefGoogle Scholar
  37. Paterson PY, Day ED, Whitacre CC, Berenberg RA, Harter DH (1981) Endogenous myelin basic protein-serum factors (MBP-SFs) and anti-MBP antibodies in humans. Occurrence in sera of clinically well subjects and patients with Multiple Sclerosis. J Neurol Sci 52: 37–51PubMedCrossRefGoogle Scholar
  38. Pham-Dinh D, Mattei MG, Nussbaum JL, Roussel G, Pontarotti P, Roeckel N, Mather IH, Artzt K, Lindahl KF, Dautigny A (1993) Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex [see comments]. Proc Natl Acad Sci USA 90: 7990–7994PubMedCrossRefGoogle Scholar
  39. Prineas JW (1985) The neuropathology of multiple sclerosis. In: Koetsier JC (ed) Handbook of clinical neurology. Elsevier, New York 337–395Google Scholar
  40. Prineas JW, Graham JS (1981) Multiple Sclerosis: capping of surface immunoglobulin G on macrophages engaged in myelin breakdown. Ann Neurol 10: 149–158PubMedCrossRefGoogle Scholar
  41. PRISMS (Prevention of Relapses and Disability by Interferon beta-la Subcutaneously in Multiple Sclerosis) Study Group (1998) Randomised double-blind placebo-controlled study of interferon beta-la in relapsing/remitting Multiple Sclerosis. Lancet 352: 1498–1504CrossRefGoogle Scholar
  42. Reindl M, Linington C, Brehm U, Egg R, Dilitz E, Deisenhammer F, Poewe W, Berger T (1999) Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in Multiple Sclerosis and other neurological diseases: a comparative study. Brain 122: 2047–2056PubMedCrossRefGoogle Scholar
  43. Rodriguez D, Della Gaspera B, Zalc B, Hauw JJ, Fontaine B, Edan G, Clanet M, Dautigny A, Pham-Dinh D (1997) Identification of a Val 145 Ile substitution in the human myelin oligodendrocyte glycoprotein: lack of association with Multiple Sclerosis. The Reseau de Recherche Clinique INSERM sur la Susceptibilite Genetique a la Sclerose en Plaques. Mult Scler 3: 377–381PubMedCrossRefGoogle Scholar
  44. Roth MP, Dolbois L, Borot N, Pontarotti P, Clanet M, Coppin H (1995) Myelin oligodendrocyte glycoprotein (MOG) gene polymorphisms and Multiple Sclerosis: no evidence of disease association with MOG. J Neuroimmunol 61: 117–122PubMedCrossRefGoogle Scholar
  45. Sadatipour BT, Greer JM, Pender MP (1998) Increased circulating antiganglioside antibodies in primary and secondary progressive Multiple Sclerosis. Ann Neurol 44: 980–983PubMedCrossRefGoogle Scholar
  46. Schluesener HJ, Sobel RA, Linington C, Weiner HL (1987) A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J Immunol 139: 4016–4021PubMedGoogle Scholar
  47. Scolding NJ, Morgan BP, Houston WA, Linington C, Campbell AK, Compston DA (1989) Vesicular removal by oligodendrocytes of membrane attack complexes formed by activated complement. Nature 339: 620–622PubMedCrossRefGoogle Scholar
  48. Seil FJ, Agrawal HC (1980) Myelin-proteolipid protein does not induce demyelinating or myelination-inhibiting antibodies. Brain Res 194: 273–277PubMedCrossRefGoogle Scholar
  49. Seil FJ, Quarles RH, Johnson D, Brady RO (1981) Immunization with purified myelin-associated glycoprotein does not evoke myelination-inhibiting or demyelinating antibodies. Brain Res 209: 470–475PubMedCrossRefGoogle Scholar
  50. Sellebjerg F, Madsen HO, Frederiksen JL, Ryder LP, Svejgaard A (1995) Acute optic neuritis: myelin basic protein and proteolipid protein antibodies, affinity, and the HLA system. Ann Neurol 38: 943–950PubMedCrossRefGoogle Scholar
  51. Storch M, Lassmann H (1997) Pathology and pathogenesis of demyelinating diseases. Curr Opin Neurol 10: 186–192PubMedCrossRefGoogle Scholar
  52. Storch MK, Piddlesden S, Haltia M, Iivanainen M, Morgan P, Lassmann H (1998a) Multiple Sclerosis: in situ evidence for antibody-and complement-mediated demyelination. Ann Neurol 43: 465–471PubMedCrossRefGoogle Scholar
  53. Storch MK, Steffen A, Brehm U, Weissert R, Wallstrom E, Kerschensteiner M, Olsson T, Linington C, Lassmann H (1998b) Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of Multiple Sclerosis pathology. Brain Pathol 8: 681–694PubMedCrossRefGoogle Scholar
  54. Sun J, Link H, Olsson T, Xiao BG, Andersson G, Ekre HP, Linington C, Diener P (1991) T and B cell responses to myelin-oligodendrocyte glycoprotein in Multiple Sclerosis. J Immunol 146: 1490–1493PubMedGoogle Scholar
  55. The IFNB Multiple Sclerosis Study Group (1993) Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43: 655–661CrossRefGoogle Scholar
  56. Tuohy VK, Yu M, Yin L, Kawczak JA, Kinkel RP (1999) Spontaneous regression of primary autoreactivity during chronic progression of experimental autoimmune encephalomyelitis and Multiple Sclerosis. J Exp Med 189: 1033–1042PubMedCrossRefGoogle Scholar
  57. Wallstrom E, Khademi M, Andersson M, Weissert R, Linington C, Olsson T (1998) Increased reactivity to myelin oligodendrocyte glycoprotein peptides and epitope mapping in HLA DR2(15)+ Multiple Sclerosis. Eur J Immunol 28: 3329–3335PubMedCrossRefGoogle Scholar
  58. Walsh MJ, Murray JM (1998) Dual implication of 2’,3’-cyclic nucleotide 3’ phosphodiesterase as major autoantigen and C3 complement-binding protein in the pathogenesis of Multiple Sclerosis. J Clin Invest 101: 1923–1931PubMedCrossRefGoogle Scholar
  59. Warren KG, Catz I (1994) Relative frequency of autoantibodies to myelin basic protein and proteolipid protein in optic neuritis and Multiple Sclerosis cerebrospinal fluid. J Neurol Sci 121: 66–73PubMedCrossRefGoogle Scholar
  60. Weinshenker BG (1995) The natural history of multiple sclerosis. Neurol Clin 13: 119–146PubMedGoogle Scholar
  61. Xiao BG, Linington C, Link H (1991) Antibodies to myelin-oligodendrocyte glycoproteinin cerebrospinal fluid from patients with Multiple Sclerosis and controls. JNeuroimmunol 31: 91–96CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • T Berger
    • 1
  • M Reindl
    • 1
  1. 1.Department of NeurologyUniversity of InnsbruckInnsbruckAustria

Personalised recommendations