Medical progress: Multiple sclerosis - The plaque and its pathogenesis

New England Journal of Medicine

Volumn 354, Issue 9, 2006, Pages 942-955

  Frohman, Elliot M ^a   Racke, Michael K ^a   Raine, Cedric S ^b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AZATHIOPRINE; BETA INTERFERON; CHEMOKINE RECEPTOR ANTAGONIST; CORTICOSTEROID; FLECAINIDE; GLATIRAMER; GLUTAMATE RECEPTOR ANTAGONIST; GROWTH FACTOR; IMMUNOGLOBULIN; JAGGED1; METHOTREXATE; MITOXANTRONE; MYELIN; NOTCH RECEPTOR; PHENYTOIN; PROTEIN NOGO; RILUZOLE; RITUXIMAB; SODIUM CHANNEL BLOCKING AGENT; INTERLEUKIN DERIVATIVE;

APOPTOSIS; BLOOD BRAIN BARRIER; CELL INFILTRATION; CENTRAL NERVOUS SYSTEM INFECTION; DEGENERATIVE DISEASE; DEMYELINATION; HISTOPATHOLOGY; HUMAN; INFLAMMATORY DISEASE; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OLIGODENDROGLIA; PATHOGENESIS; PLASMAPHERESIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; ANIMAL; B LYMPHOCYTE; BRAIN; DISEASE COURSE; IMMUNOLOGY; MYELIN SHEATH; NERVE FIBER; PATHOLOGY; PHYSIOLOGY; ULTRASTRUCTURE;

ANIMALS; AXONS; B-LYMPHOCYTES; BRAIN; DISEASE PROGRESSION; HUMANS; INTERLEUKINS; MULTIPLE SCLEROSIS; MYELIN SHEATH; T-LYMPHOCYTES;

EID: 33644607018     PISSN: 00284793     EISSN: None     Source Type: Journal    
DOI: 10.1056/NEJMra052130     Document Type: Review

References (78)

1. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000;343:938-52.
2. Goodin DS, Frohman EM, Garmany GP Jr, et al. Disease modifying therapies in multiple sclerosis. Neurology 2002;58:169-78.
3. [Erratum, Neurology 2002;59:480.]
4. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;338:278-85.
5. Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Brück W. Acute axonal injury in multiple sclerosis: correlation with demyelination and inflammation. Brain 2000;123:1174-83.
6. Kornek B, Storch MK, Weissert R, et al. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol 2000;157:267-76.
7. Raine CS. The Dale E. McFarlin Memorial Lecture: the immunology of the multiple sclerosis lesion. Ann Neurol 1994;36:Suppl:S61-S72.
8. Geurts JJ, Bo L, Pouwels PJ, Castelijns JA, Polman CH, Barkhof F. Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. AJNR Am J Neuroradiol 2005;26:572-7.
9. Pettinelli CB, McFarlin DE. Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt 1+ 2- T lymphocytes. J Immunol 1981;127:1420-3.
10. Ando DG, Clayton J, Kono D, Urban JL, Sercarz EE. Encephalitogenic T cells in the B10.PL model of experimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype. Cell Immunol 1989;124:132-43.
11. Huseby ES, Liggitt D, Brabb T, Schnabel B, Ohlen C, Goverman J. A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. J Exp Med 2001;194:669-76.
12. Scholz C, Patton KT, Anderson DE, Freeman GJ, Hafler DA. Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. J Immunol 1998;160:1532-8.
13. Lovett-Racke AE, Trotter JL, Lauber J, Perrin PJ, June CH, Racke MK. Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients: a marker of activated/memory T cells. J Clin Invest 1998;101:725-30.
14. [Erratum, J Clin Invest 1998;101:1542.]
15. Crawford MP, Yan SX, Ortega SB, et al. 2004. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay. Blood 2004;103:4222-31.
16. Kivisakk P, Mahad DJ, Callahan MK, et al. Expression of CCR7 in multiple sclerosis: implications for CNS immunity. Ann Neurol 2004;55:627-38.
17. Zang YC, Li S, Rivera VM, et al. Increased CD8+ cytotoxic T cell responses to myelin basic protein in multiple sclerosis. J Immunol 2004;172:5120-7.
18. Bielekova B, Goodwin B, Richert N, et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat Med 2000;6:1167-75.
19. [Erratum, Nat Med 2000;6:1412.]
20. Kappos L, Comi G, Panitch H, et al. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. Nat Med 2000;6:1176-82.
21. [Erratum, Nat Med 2001;7:129.]
22. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145-73.
23. Farrar JD, Murphy KM. Type I interferons and T helper development. Immunol Today 2000;21:484-9.
24. Dhib-Jalbut S. Mechanisms of action of interferons and glatiramer acetate in multiple sclerosis. Neurology 2002;58:Suppl 4:S3-S9.
25. Wandinger KP, Sturzebecher CS, Bielekova B, et al. Complex immunomodulatory effects of interferon-beta in multiple sclerosis include the upregulation of T helper 1-associated marker genes. Ann Neurol 2001;50:349-57.
26. Trinchieri G, Pflanz S, Kastelein RA. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 2003;19:641-4.
27. Zhang GX, Gran B, Yu S, et al. Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J Immunol 2003;170:2153-60.
28. Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421:744-8.
29. Lock C, Hermans G, Pedotti R, et al. Gene microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002;8:500-8.
30. Lovett-Racke AE, Rocchini AE, Choy J, et al. Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. Immunity 2004;21:719-31.
31. Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med 2004;200:79-87.
32. Chitnis T, Najafian N, Benou C, et al. Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. J Clin Invest 2001;108:739-47.
33. Qin Y, Duquette P, Zhang Y, Talbot P, Poole R, Antel J. Clonal expansion and somatic hypermutation of V(H) genes of B cells from cerebrospinal fluid in multiple sclerosis. J Clin Invest 1998;102:1045-50.
34. Owens GP, Ritchie AM, Burgoon MP, Williamson RA, Corboy JR, Gilden DH. Single-cell repertoire analysis demonstrates that clonal expansion is a prominent feature of the B cell response in multiple sclerosis cerebrospinal fluid. J Immunol 2003;171:2725-33.
35. Monson NL, Brezinschek HP, Brezinschek RI, et al. Receptor revision and atypical mutational characteristics in clonally expanded B cells from the cerebrospinal f luid of recently diagnosed multiple sclerosis patients. J Neuroimmunol 2005;158:170-81.
36. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 2004;199:971-9.
37. Balashov KE, Khoury SJ, Hafler DA, Weiner HL. Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis. J Clin Invest 1995;95:2711-9.
38. Waldner H, Collins M, Kuchroo VK. Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease. J Clin Invest 2004;113:990-7.
39. Deng C, Radu C, Diab A, et al. IL-1 receptor-associated kinase 1 (IRAK1) regulates susceptibility to organ-specific autoimmunity. J Immunol 2003;170:2833-42.
40. Kerfoot SM, Long EM, Hickey MJ, et al. TLR4 contributes to disease-inducing mechanisms resulting in central nervous system autoimmune disease. J Immunol 2004;173:7070-7.
41. Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N. Prevention of experimental allergic encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992;356:63-6.
42. Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003;348:15-23.
43. Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 2005;353:375-81.
44. Kleinschmidt-DeMasters BK, Tyler KL. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 2005;353:369-74.
45. Van Assche G, Van Ranst M, Sciot R, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease. N Engl J Med 2005;353:362-8.
46. Chabas D, Baranzini SE, Mitchell D, et al. The influence of the pro-inflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science 2001;294:1731-5.
47. Raine CS. Demyelinating diseases. In: Davis RL, Robertson DM, eds. Textbook of neuropathology. 2nd ed. Baltimore: Williams & Wilkins, 1991:535-620.
48. Genain CP, Cannella B, Hauser SL, Raine CS. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med 1999;5:170-5.
49. Raine CS, Scheinberg L, Waltz JM. Multiple sclerosis: oligodendrocyte survival and proliferation in an active, established lesion. Lab Invest 1981;45:534-46.
50. Prineas JW, Graham JS. Multiple sclerosis: capping of surface immunoglobulin G on macrophages engaged in myelin breakdown. Ann Neurol 1981;10:149-58.
51. Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000;47:707-17.
52. Lucchinetti CF, Brück W, Rodriguez M, Lassmann H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol 1996;6:259-74.
53. Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. A quantitative analysis of oligodendrocytes in multiple sclerosis lesions: a study of 113 cases. Brain 1999;122:2279-95.
54. Barnett MH, Prineas JW. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 2004;55:458-68.
55. Wilkins A, Majed H, Layfield R, Compston A, Chandran S. Oligodendrocytes promote neuronal survival and axonal length by distinct intracellular mechanisms: a novel role for oligodendrocyte-derived glial cell line-derived neurotrophic factor. J Neurosci 2003;23:4967-74.
56. Waxman SG, Craner MJ, Black JA. Sodium channel expression along axons in multiple sclerosis and its models. Trends Pharmacol Sci 2004;25:584-91.
57. Bechtold DA, Kapoor R, Smith KJ. Axonal protection using flecainide in experimental autoimmune encephalomyelitis. Ann Neurol 2004;55:607-16.
58. Lo AC, Saab CY, Black JA, Waxman SG. Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo. J Neurophysiol 2003;90:3566-71.
59. Ferguson B, Matyszak MK, Esiri MM, Perry VH. Axonal damage in multiple sclerosis lesions. Brain 1997;120:393-9.
60. Bjartmar C, Wujek JR, Trapp BD. Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 2003;206:165-71.
61. Werner P, Pitt D, Raine CS. Multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Ann Neurol 2001;50:169-80.
62. Diestel A, Aktas O, Hackel D, et al. Activation of microglial poly(ADP-ribose)-polymerase-1 by cholesterol breakdown products during neuroinflammation: a link between demyelination and neuronal damage. J Exp Med 2003;198:1729-40.
63. Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol 2000;48:893-901.
64. van Waesberghe JH, Kamphorst W, De Groot CJ, et al. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol 1999;46:747-54.
65. Kalkers NF, Barkhof F, Bergers E, van Schijndel R, Polman CH. The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study. Mult Scler 2002;8:532-3.
66. Wang KC, Kim JA, Sivasankaran R, Segal R, He Z. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG, and OMgp. Nature 2002;420:74-8.
67. Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES. Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 1993;33:137-51.
68. Scolding N, Franklin R, Stevens S, Heldin CH, Compston A, Newcombe J. Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain 1998;121:2221-8.
69. Wolswijk G. Oligodendrocyte survival, loss and birth in lesions of chronicstage multiple sclerosis. Brain 2000;123:105-15.
70. Capello E, Voskuhl RR, McFarland HF, Raine CS. Multiple sclerosis: re-expression of a developmental gene in chronic lesions correlates with remyelination. Ann Neurol 1997;41:797-805.
71. Arnett HA, Fancy SP, Alberta JA, et al. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science 2004;306:2111-5.
72. Omari KM, John GR, Sealfon SC, Raine CS. CXC chemokine receptors on human oligodendrocytes: implications for multiple sclerosis. Brain 2005;128:1003-15.
73. Mi S, Miller RH, Lee X, et al. LINGO-1 negatively regulates myelination by oligodendrocytes. Nat Neurosci 2005;8:745-51.
74. John GR, Shankar SL, Shafit-Zagardo B, et al. Multiple sclerosis: re-expression of a developmental pathway that restricts remyelination. Nat Med 2002;8:1115-21.
75. Dowling P, Shang G, Raval S, Menonna J, Cook S, Husar W. Involvement of the CD95 (APO-1/ Fas) receptor/ligand system in multiple sclerosis brain. J Exp Med 1996;184:1513-8.
76. Frohman EM, Zhang H, Kramer PD, et al. MRI characteristics of the MLF in MS patients with chronic internuclear ophthalmoparesis. Neurology 2001;57:762-8.
77. Frohman EM, Goodin DS, Calabresi PA, et al. The utility of MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003;61:602-11.
78. Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Magnetization transfer ratio and mean diffusivity of normal appearing white and gray matter from patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2001;70:311-7.