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Immunology of multiple sclerosis

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Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelin-reactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by meningeal lymphoid follicles with germinal centers.

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References and Recommended Reading

  1. Confavreux C, Vukusic S: Natural history of multiple sclerosis: a unifying concept. Brain 2006, 129:606–616.

    Article  PubMed  Google Scholar 

  2. Gold R, Linington C, Lassmann H: Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006, 129:1953–1971.

    Article  PubMed  Google Scholar 

  3. Brück W: The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage. J Neurol 2005, 252(Suppl 5):v3–v9.

    Article  PubMed  CAS  Google Scholar 

  4. Kutzelnigg A, Lucchinetti CF, Stadelmann C, et al.: Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005, 128:2705–2712.

    Article  PubMed  Google Scholar 

  5. Kutzelnigg A, Rauschka H, Stadelmann C, et al.: Pathological substrate of disease progression in multiple sclerosis. J Neuroimmunol 2004, 154:189.

    Google Scholar 

  6. Serafini B, Rosicarelli B, Magliozzi R, et al.: Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004, 14:164–174.

    Article  PubMed  Google Scholar 

  7. Armengol MP, Juan M, Lucas-Martín A, et al.: Thyroid autoimmune disease: demonstration of thyroid antigen-specific B cells and recombination-activating gene expression in chemokine-containing active intrathyroidal germinal centers. Am J Pathol 2001, 159:861–873.

    PubMed  CAS  Google Scholar 

  8. Freedman MS, Thompson EJ, Deisenhammer F, et al.: Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis. Arch Neurol 2005, 62:865–870.

    Article  PubMed  Google Scholar 

  9. Oksenberg JR, Barcellos LF: Multiple sclerosis genetics: leaving no stone unturned. Genes Immun 2005, 6:375–387.

    Article  PubMed  CAS  Google Scholar 

  10. Barcellos LF, Sawcer S, Ramsay PP, et al.: Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. Hum Mol Genet 2006, 15:2813–2824.

    Article  PubMed  CAS  Google Scholar 

  11. Greer JM, Pender MP: The presence of glutamic acid at positions 71 or 74 in pocket 4 of the HLA-DRβ1 chain is associated with the clinical course of multiple sclerosis. J Neurol Neurosurg Psychiatry 2005; 76:656–662.

    Article  PubMed  CAS  Google Scholar 

  12. McCombe PA, Chalk JB, Pender MP: Familial occurrence of multiple sclerosis with thyroid disease and systemic lupus erythematosus. J Neurol Sci 1990, 97:163–171.

    Article  PubMed  CAS  Google Scholar 

  13. Henderson RD, Bain CJ, Pender MP: The occurrence of autoimmune diseases in patients with multiple sclerosis and their families. J Clin Neurosci 2000, 7:434–437.

    Article  PubMed  CAS  Google Scholar 

  14. Bias WB, Reveille JD, Beaty TH, et al.: Evidence that autoimmunity in man is a Mendelian dominant trait. Am J Hum Genet 1986, 39:584–602.

    PubMed  CAS  Google Scholar 

  15. Barcellos LF, Kamdar BB, Ramsay PP, et al.: Clustering of autoimmune diseases in families with a high risk for multiple sclerosis: a descriptive study. Lancet Neurol 2006, 5:924–931.

    Article  PubMed  CAS  Google Scholar 

  16. Sospedra M, Martin R: Immunology of multiple sclerosis. Annu Rev Immunol 2005, 23:683–747.

    Article  PubMed  CAS  Google Scholar 

  17. Greer JM, Csurhes PA, Cameron KD, et al.: Increased immunoreactivity to two overlapping peptides of myelin proteolipid protein in multiple sclerosis. Brain 1997, 120:1447–1460.

    Article  PubMed  Google Scholar 

  18. Pender MP, Csurhes PA, Greer JM, et al.: Surges of increased T cell reactivity to an encephalitogenic region of myelin proteolipid protein occur more often in patients with multiple sclerosis than in healthy subjects. J Immunol 2000, 165:5322–5331.

    PubMed  CAS  Google Scholar 

  19. Raine CS, Cannella B, Hauser SL, Genain CP: Demyelination in primate autoimmune encephalomyelitis and acute multiple sclerosis lesions: a case for antigen-specific antibody mediation. Ann Neurol 1999, 46:144–160.

    Article  PubMed  CAS  Google Scholar 

  20. Lucchinetti C, Brück W, Parisi J, et al.: Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000, 47:707–717.

    Article  PubMed  CAS  Google Scholar 

  21. Greer JM, Pender MP: Antibodies specific for myelin proteolipid protein are of potential pathogenic relevance in myelin opsonization in multiple sclerosis. Clin Immunol 2005, 115(Suppl 1):S91.

    Google Scholar 

  22. Zhou D, Srivastava R, Nessler S, et al.: Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis. Proc Natl Acad Sci U S A 2006, 103:19057–19062.

    Article  PubMed  CAS  Google Scholar 

  23. Sadatipour BT, Greer JM, Pender MP: Increased circulating antiganglioside antibodies in primary and secondary progressive multiple sclerosis. Ann Neurol 1998, 44:980–983.

    Article  PubMed  CAS  Google Scholar 

  24. Pender MP, Csurhes PA, Wolfe NP, et al.: Increased circulating T cell reactivity to GM3 and GQ1b gangliosides in primary progressive multiple sclerosis. J Clin Neurosci 2003, 10:63–66.

    Article  PubMed  CAS  Google Scholar 

  25. Marconi S, Acler M, Lovato L, et al.: Anti-GD2-like IgM autoreactivity in multiple sclerosis. Mult Scler 2006, 12:302–308.

    Article  PubMed  CAS  Google Scholar 

  26. Lucchinetti CF, Mandler RN, McGavern D, et al.: A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 2002, 125:1450–1461.

    Article  PubMed  Google Scholar 

  27. Lennon VA, Kryzer TJ, Pittock SJ, et al.: IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005, 202:473–477.

    Article  PubMed  CAS  Google Scholar 

  28. Villar LM, Masjuan J, GonzálezPorqué P, et al.: Intrathecal IgM synthesis is a prognostic factor in multiple sclerosis. Ann Neurol 2003, 53:222–226.

    Article  PubMed  CAS  Google Scholar 

  29. Cepok S, Jacobsen M, Schock S, et al.: Patterns of cerebrospinal fluid pathology correlate with disease progression in multiple sclerosis. Brain 2001, 124:2169–2176.

    Article  PubMed  CAS  Google Scholar 

  30. Qin Y, Duquette P, Zhang Y, et al.: Clonal expansion and somatic hypermutation of VH genes of B cells from cerebrospinal fluid in multiple sclerosis. J Clin Invest 1998, 102:1045–1050.

    PubMed  CAS  Google Scholar 

  31. Cepok S, Zhou D, Srivastava R, et al.: Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis. J Clin Invest 2005, 115:1352–1360.

    Article  PubMed  CAS  Google Scholar 

  32. Williamson RA, Burgoon MP, Owens GP, et al.: Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis. Proc Natl Acad Sci U S A 2001, 98:1793–1798.

    Article  PubMed  CAS  Google Scholar 

  33. Collard RC, Koehler RP, Mattson DH: Frequency and significance of antinuclear antibodies in multiple sclerosis. Neurology 1997, 49:857–861.

    PubMed  CAS  Google Scholar 

  34. Villar LM, Sádaba MC, Roldán E, et al.: Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. J Clin Invest 2005, 115:187–194.

    Article  PubMed  CAS  Google Scholar 

  35. Correale J, Fiol M, Gilmore W: The risk of relapses in multiple sclerosis during systemic infections. Neurology 2006, 67:652–659.

    Article  PubMed  CAS  Google Scholar 

  36. Pender MP: Infection of autoreactive B lymphocytes with EBV, causing chronic autoimmune diseases. Trends Immunol 2003, 24:584–588.

    Article  PubMed  CAS  Google Scholar 

  37. Pender MP: Epstein-Barr virus and autoimmunity. In Infection and Autoimmunity. Edited by Shoenfeld Y, Rose NR. Amsterdam: Elsevier; 2004:163–170.

    Google Scholar 

  38. Ascherio A, Munch M: Epstein-Barr virus and multiple sclerosis. Epidemiology 2000, 11:220–224.

    Article  PubMed  CAS  Google Scholar 

  39. Wandinger KP, Jabs W, Siekhaus A, et al.: Association between clinical disease activity and Epstein-Barr virus reactivation in MS. Neurology 2000, 55:178–184.

    PubMed  CAS  Google Scholar 

  40. Pohl D, Krone B, Rostasy K, et al.: High seroprevalence of Epstein-Barr virus in children with multiple sclerosis. Neurology 2006, 67:2063–2065.

    Article  PubMed  CAS  Google Scholar 

  41. Thacker EL, Mirzaei F, Ascherio A: Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis. Ann Neurol 2006, 59:499–503.

    Article  PubMed  Google Scholar 

  42. Levin LI, Munger KL, Rubertone MV, et al.: Temporal relationship between elevation of Epstein-Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA 2005, 293:2496–2500.

    Article  PubMed  CAS  Google Scholar 

  43. Pender MP: Genetically determined failure of activation-induced apoptosis of autoreactive T cells as a cause of multiple sclerosis. Lancet 1998, 351:978–981.

    PubMed  CAS  Google Scholar 

  44. Pender MP, Nguyen KB, McCombe PA, Kerr JFR: Apoptosis in the nervous system in experimental allergic encephalomyelitis. J Neurol Sci 1991, 104:81–87.

    Article  PubMed  CAS  Google Scholar 

  45. Tabi Z, McCombe PA, Pender MP: Apoptotic elimination of Vβ8.2+ cells from the central nervous system during recovery from experimental autoimmune encephalomyelitis induced by the passive transfer of Vβ8.2+ encephalitogenic T cells. Eur J Immunol 1994, 24:2609–2617.

    Article  PubMed  CAS  Google Scholar 

  46. Pender MP, Rist MJ: Apoptosis of inflammatory cells in immune control of the nervous system: role of glia. Glia 2001, 36:137–144.

    Article  PubMed  CAS  Google Scholar 

  47. James JA, Kaufman KM, Farris AD, et al.: An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. J Clin Invest 1997, 100:3019–3026.

    Article  PubMed  CAS  Google Scholar 

  48. Polman CH, O’Connor PW, Havrdova E, et al.: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006, 354:899–910.

    Article  PubMed  CAS  Google Scholar 

  49. Berger JR, Koralnik IJ: Progressive multifocal leukoencephalopathy and natalizumab: unforeseen consequences. N Engl J Med 2005, 353:414–416.

    Article  PubMed  CAS  Google Scholar 

  50. Pender MP, Wolfe NP: Prevention of autoimmune attack and disease progression in multiple sclerosis: current therapies and future prospects. Intern Med J 2002, 32:554–563.

    Article  PubMed  CAS  Google Scholar 

  51. Diamond MC, Scheibel AB, Elson LM: The Human Brain Coloring Book. New York: HarperCollins; 1985.

    Google Scholar 

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Authors and Affiliations

  1. Neuroimmunology Research Centre, Clinical Sciences Building, Royal Brisbane and Women’s Hospital, Herston, Queensland, 4029, Australia

    Michael P. Pender MD, PhD, FRACP

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  1. Michael P. Pender MD, PhD, FRACP
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  2. Judith M. Greer PhD
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Correspondence to Michael P. Pender MD, PhD, FRACP.

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Pender, M.P., Greer, J.M. Immunology of multiple sclerosis. Curr Allergy Asthma Rep 7, 285–292 (2007). https://doi.org/10.1007/s11882-007-0043-x

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