A 21 Point Unifying Hypothesis on the Etiology and Treatment of Multiple Sclerosis

Canadian Journal of Neurological Sciences

Volumn 25, Issue 2, 1998, Pages 93-101

  Weiner, Howard L ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIGEN; MYELIN;

AUTOIMMUNITY; CELLULAR IMMUNITY; CLINICAL FEATURE; CROSS REACTION; IMMUNOPATHOGENESIS; IMMUNOREGULATION; MULTIPLE SCLEROSIS; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SENSITIZATION; TREATMENT OUTCOME; VIRUS INFECTION;

HUMANS; MULTIPLE SCLEROSIS; NEUROIMMUNOMODULATION;

EID: 0031808312     PISSN: 03171671     EISSN: None     Source Type: Journal    
DOI: 10.1017/S0317167100033680     Document Type: Review

References (98)

1. Martin R, McFarland HF and McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol 1992; 10: 153-187.
2. Raine CS. The Dale McFarlin memorial lecture. The immunology of the MS lesion. Ann Neurol 1994; 36: S61-S72.
3. Prineas JW. Pathology of Multiple Sclerosis. In: S. D. Cook eds. Handbook of Multiple Sclerosis. Newark: Marcel Dekker, Inc., 1996: 223-255.
4. Lassmann H. Comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis. eds. Berlin: Springer-VerlaG, 1983.
5. Windhagen A, Newcombe J, Dangond F, et al. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med 1995; 182: 1985-1996.
6. Olsson T, Wang W-Z, Höjeberg B, et al. Autoreactive T-lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma. J Clin Invest 1990; 86: 981-985.
7. Allegretta M, Nicklas J, Sriram S, Albertini R. T cells responsive to myelin basic protein in patients with multiple sclerosis. Science 1990; 247: 718.
8. Zhang J, Markovic S, Raus J, et al. Increased frequency of IL-2 responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 1993; 179: 973-984.
9. Bieganowska KD, Ausubel LJ, Modabber Y, et al. Direct ex vivo analysis of activated, fas-sensitive autoreactive T cells in human autoimmune disease. J Exp Med 1997; 185: 1585-1594.
10. Warren KG, Catz I, Johnson E, Mielke B. Anti-myelin basic protein and anti-proteolipid protein specific forms of multiple sclerosis. Ann of Neurol 1994; 35: 280-289.
11. Linington C, Bradi M, Lassmann H, Brunner C, Vass K. Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 1988; 130: 443-454.
12. Schluesener H, Sobel R, Linington C, Weiner HL. A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in CNS autoimmune disease. J Immunol 1987; 139: 4016-4021.
13. Lehmann P, Forsthuber T, Miller A, Sercarz E. Spreading of T-cell autoimmunity to ćyptic determinants of an autoantigen. Nature 1992; 358: 155.
14. McCarron R, Fallis R, McFarlin D. Alterations in T cell antigen specificity and class II restriction during the course of chronic relapsing experimental allergic encephlomyelitis. J Neuroimmunol 1990; 29: 73-79.
15. Cross AH, Tuohy VK, Raine CS. Development of reactivity to new myelin antigens during chronic relapsing autoimmune demyelination. Cell Immunol 1993; 146: 261-270.
16. Kaufman DI, Clare-Salzler M, Tian, et al. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 1993; 366: 69-72.
17. Tisch R, Yang X-D, Singer SM, et al. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 1993; 366: 72-75.
18. Kerlero de Rosbo N, Milo R, Lees MB, et al. Reactivity to myelin antigens in multiple sclerosis: peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein. J Clin Invest 1993; 92: 2602-2608.
19. Harrison LC. Islet cell antigens in insulin-dependent diabetes: Pandora's box revisited. Immunol Today 1992; 13: 348-352.
20. Shimonkevitz R, Colburn C, Burnham J, Murray RS, Kotzin BL. Clonal expansion of activated gamma/delta T cells in recent onset multiple sclerosis. Proc NatI Acad Sci USA 1993; 90: 923-927.
21. Wucherpfennig KW, Newcombe J, Kebby C, Cuzner ML, Hafler DA. Gamma/delta T cell receptor repertoire in acute demyelinating multiple sclerosis lesions. Proc Natl Acad Sci U S A 1992; 89: 4588-4592.
22. Panitch HS, Hirsch RL, Haley AS, Johnson KP. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1987; 1: 893-895.
23. Seder RA, Paul WE. Lymphocyte responses and cytokines. Cell 1994; 76: 241-251.
24. Racke MK, Bonomo A, Scott DE, et al. Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease. J Exp Med 1994; 180: 1961-1966.
25. Groux H, O'Garra A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389: 737-742.
26. Chen Y, Kuchroo VK, Inobe J-I, Hafler DA, Weiner HL. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 1994; 265: 1237-1240.
27. Khoury SJ, Hancock WW, Weiner HL. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis as associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor β, interleukin 4, and prostaglandin E expression in the brain. J Exp Med 1992; 176: 1355-1364.
28. Karpus W, Swanborg R. CD4+ suppressor cells inhibit the function of effector cells of experimental autoimmune encephalomyelitis through a mechanism involving transforming growth factor beta. J Immunol 1991; 146: 1163-1168.
29. Steinman L. Multiple sclerosis and its animal models: the role of the major histocompatibility complex and the T cell receptor repertoire. Semin Immunopathol 1992; 14: 79-93.
30. Zipp F, Weber F, Huber S, et al. Genetic control of multiple sclerosis: increased production of lymphotoxin and tumor necrosis factor-α by HLA-DR2+ T cells. Ann Neurol 1995; 38: 723-730.
31. Segal BM, Shevach EM. IL-12 unmasks latent autoimmune disease in resistant mice. J Exp Med 1996; 184: 771-775.
32. Maron R, Hancock W, Slavin A, et al. Genetic susceptibility or resistance to EAE in MHC identical mice is linked to differential cytokine production. FASEB 1997; LB60 (Abst):
33. Mussener A, Lorentzen JC, Kleinau S, Klareskog L. Altered Th1/Th2 balance associated with non-major histocompatibility complex genes in collagen-induced arthritis in resistant rat strains. Eur J Immunol 1997; 27: 695-699.
34. Kuchroo V, Prabhu Das M, Brown JA, et al. B7-1 and B7-2 costimulatory molecules differentially activate the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 1995; 80: 707-718.
35. Oro AS, Guarino TJ, Driver R, Steinman L, Umetsu DT. Regulation of disease susceptibility: decreased prevalence of IgE- mediated allergic disease in patients with multiple sclerosis. J Allergy Clin Immunol 1996; 97: 1402-1408.
36. Sadovnick AD, Rice GP, Armstrong H. A population-based study of multiple sclerosis in twins: update. Ann Neurol 1993; 33: 281-285.
37. Kurtzke JF. Epidemiology of multiple sclerosis. In: Vinken PJ, Bruyn GW, Klawans HL, et al., eds. Handbook of Clinical Neurology. New York: Elsevier Science Publishers, 1985: 259-287.
38. Bamford CR, Sibley WA, Thies C. Seasonal variation of multiple sclerosis exacerbations in Arizona. Neurology 1983; 33: 897-701.
39. Balashov KE, Olek MJ, Khoury SJ, Weiner HL. Seasonal variation of IFN-γ production in progressive multiple sclerosis. AAN 1998 Scientific Program: Neurology (Abst) 1998.
40. Cook SD, Rohowsky-Kochan C, Bansil S, Dowling PC. Evidence for a viral etiology of multiple sclerosis. In: Cook SD, eds. Handbook of Multiple Sclerosis. Newark: Marcel Dekker, Inc., 1996: 97-118.
41. Antel J, Arnason B, Medof M. Suppressor cell function in multiple sclerosis: correlation with clinical disease activity. Ann Neurol 1978; 5: 338-342.
42. Hafler DA, Weiner HL. Immunologic mechanisms and therapy in multiple sclerosis. Immunol Rev 1995; 144: 75-107.
43. Hafler DA, Weiner HL. In vivo labeling of peripheral blood T-cells using monoclonal antibodies: rapid traffic into cerebrospinal fluid in multiple sclerosis. Ann Neurol 1987; 22: 90-93.
44. Bongioanni P, Meucci G. T-cell tumor necrosis factor-alpha receptor binding in patients with multiple sclerosis. Neurology 1997; 48: 826-831.
45. Noronha A, Toscas A, Jensen MA. Interferon beta augments suppressor cell function in multiple sclerosis. Ann Neurol 1990; 27: 207-210.
46. Hafler D, Fox D, Manning M, et al. In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. N Engl J Med 1985; 312: 1405-1411.
47. Berger T, Weerth S, Kojima K, et al. Experimental autoimmune encephalomyelitis: The antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system. Laboratory Investigation 1997; 76: 355-364.
48. Revesz T, Kidd D, Thompson AJ, et al. A comparison of the pathology of primary and secondary progressive multiple sclerosis. Brain 1994; 117: 759-765.
49. Schmied M, Breitschopf H, Gold R, et al. Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am J Pathol 1993; 143: 446-452.
50. Kennedy MK, Torrance DS, Picha KS, Mohler KM. Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. J Immunol 1992; 149: 2496-2505.
51. Chen Y, Hancock WW, Marks R, Gonnella PA. Weiner HL. Mechanisms of recovery from experimental allergic encephalomyelitis: T cell deletion and immune deviation in myelin basic protein receptor transgenic mice. J Neuroimmunol 1998; in press.
52. Correale J, Gilmore W, McMillan M, et al. Patterns of cytokine secretion by autoreactive proteolipid protein-specific T cell clones during the course of multiple sclerosis. J Immunol 1995; 154: 2959-2968.
53. Balashov KE, Smith DR, Khoury SJ, Hafler DA, Weiner HL. Increased IL-12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand. Proc Natl Acad Sci U S A 1997; 94: 599-603.
54. Comabella M, Balashov K, Smith D, Weiner HL, Khoury SJ. Cyclophosphamide treatment normalizes the increased IL-12 production in patients with chronic progressive MS and induces a Th2 cytokine switch. AAN Scientific Program: Neurology (Abst) 1998.
55. Miller DH, Grossman RI, Reingold SC, McFarland HF. The role of magnetic resonance techniques in understanding and managing multiple sclerosis. Brain (1998); 121: 3-24.
56. Khoury SJ, Guttman CRG, Orav EJ, et al. Longitudinal MRI imaging in multiple sclerosis: correlation between disability and lesion burden. Neurology 1994; 44: 2120-2124.
57. Filippi M, Horsfield MA, Morrissey SP. Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis. Neurology 1994; 44: 635-641.
58. Weiner HL, Khoury SJ, Guttmann C, et al. Magnetic resonance imaging correlates with clinical disability and attacks in multiple sclerosis. AAN Scientific Program: Neurology (Abst) 1998.
59. Losseff NA, et al. Spinal cord atrophy and disability in multiple sclerosis: A new reproducible and sensitive MRI technique with potential to monitor disease progression. Brain 1996; 119: 101-108.
60. van Walderveen MA, Barkhof F, Hommes OR, et al. Correlating MRI and clinical disease activity in multiple sclerosis: relevance of hypointense lesions on short-TR/short-TE (T1-weighted) spin-echo images. Neurology 1995; 45: 1684-1690.
61. Martin R, McFarland HF. Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis. Crit Rev Clin Lab Sci 1995; 32: 121-182.
62. Lublin FD, Knobler RL, Kalman B, et al. Monoclonal anti-gamma Interferon antibodies enhance experimental allergic encephalomyelitis. Autoimmunity 1993; 16: 267-274.
63. Ferber IA, Brocke S, Taylor-Edwards C, et al. Mice with disrupted IFN-γ gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunology 1996; 156: 5-7.
64. Billiau A, Heremans H, Vandekerckhove F, et al. Enhancement of experimental allergic encephalomyelitis by antibodies against IFN-γ. J Immunol 1988; 140: 1506-1510.
65. Weiner H, Hohol M, Khoury S, Dawson D, Hafler D, Therapy for MS. Neurologic Clinics 1995; 13: 173-196.
66. Hohol MJ, Olek MJ, Orav EJ, et al. Treatment of progressive multiple sclerosis with pulse cyclophosphamide/methylprednisolone: response to therapy is linked to duration of progressive disease. AAN Scientific Program: Neurology (Abst) 1998.
67. Weiner HL. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 1997; 18: 335-343.
68. Fukaura H, Kent SC, Pietrusewicz MJ, et al. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. J Clin Invest 1996; 98; 70-77.
69. Nicholson L, Greer J, Sobel R, Lees M, Kuchroo V. An altered peptide ligand mediates immune deviation and prevents EAE. Immunity 1995; 3: 397-405.
70. Miller A, Lider O, Weiner HL. Antigen-driven bystander suppression following oral administration of antigens. J Exp Med 1991; 174: 791-798.
71. Al-Sabbagh A, Miller A, Santos LMB, Weiner HL. Antigen-driven tissue-specific suppression following oral tolerance: orally administered myelin basic protein suppresses proteolipid induced experimental autoimmune encephalomyelitis in the SJL mouse. EurJ Immunol 1994; 24: 2104-2109.
72. von Herrath MG, Dyrberg T, Oldstone MBA. Oral insulin treatment suppresses virus-induced antigen-specific destruction of beta cells and prevents autoimmune diabetes in transgenic mice. J Clin Invest 1996; 98: 1324-1331.
73. Becker KJ, McCarron RM, Ruetzler C, et al. Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia. Proc Natl Acad Sci U S A 1997; 94: 10873-10878.
74. Aharoni R, Teitelbaum D, Sela M, Arnon R. Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Science, USA 1997; 94: 10821-10826.
75. Smith D, Balshov K, Hafler D, Khoury S, Weiner H. Immune deviation following cyclophosphamide/ methylprednisolone treatment of multiple sclerosis: Increased IL-4 and associated eosinophilia. Ann Neurol 1997; 42: 313-318.
76. Rudick R, Ransohoff R, Peppler R. Interferon beta induces IL-10 expression: relevance to multiple sclerosis. Ann Neurol 1996; 40: 618-627.
77. Takashima H, Smith DR, Fukaura H, et al. Cyclophosphamide induces myelin antigen specific IL-4 secreting T cells in multiple sclerosis patients. Clin Immunol Immunopath 1998: in press.
78. Genc K, Dona D, Reder AT. Increased CD80+ B cells in active multiple sclerosis and reversal by interferon β-1b therapy. J Clin Invest 1997; 99: 2664-2671.
79. Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998; 338; 278-285.
80. Sriram S, Rodriguez M. Indictment of the microglia as the villain in multiple sclerosis. Neurology 1997; 48: 464-470.
81. Yudkin PL, Ellison GW, Ghezzi A, et al. Overview of azathioprine treatment in multiple sclerosis. The Lancet 1991; 338: 1051-1055.
82. Durelli L, Bongioanni MR, Ferrero B, et al. Interferon alpha-2a treatment of relapsing-remitting multiple sclerosis: disease activity resumes after stopping treatment. Neurology 1996; 47: 123-129.
83. Jacobs L, Cookfair D, Rudick R, et al. Results of a phase III trial of intramuscular recombinant beta interferon as treatment for multiple sclerosis. Ann Neurol 1994; 36: 259.
84. The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Interferon beta-1b in the treatment of multiple sclerosis: Final outcome of the randomized controlled trial. Neurology 1995; 45: 1277-1285.
85. Beutler E, Sipe JC, Romine JS, et al. The treatment of chronic progressive multiple sclerosis with cladribine. Proc Natl Acad Sci U S A 1996; 93: 1716-1720.
86. Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: Results of a phase III multicenter, double-blind, placebo-controlled trial. Neurology 1995; 45: 1268-1276.
87. Beck RW, Cleary PA, Trobe JD, et al. The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. NEJM 1993; 239: 1764-1769.
88. Weiner HL, Mackin GA, Orav EJ, et al. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology 1993; 43: 910-918.
89. Hommes OR, Lamers KJB, Reekers P. Effect of intensive immuno-suppression on the course of chronic progressive multiple sclerosis. J Neurol 1980; 223: 177-190.
90. Multiple Sclerosis Study Group. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. Ann Neurol 1990; 27: 591-605.
91. Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B. Randomized placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Lancet 1997; 349: 589-593.
92. Anderson O, Lycke J, Tollesson PO, et al. Linomide reduces the rate of active lesions in relapsing-remitting multiple sclerosis. Neurology 1996; 47: 895-900.
93. Karussis DM, Meiner Z, Lehmann D, et al. Treatment of secondary progressive multiple sclerosis with the immunomodulator linomide: a double blind, placebo-controlled pilot study with monthly magnetic resonance imaging evaluation. Neurology 1996; 47: 341-346.
94. Goodkin DE, Rudick RA, VanderBrug Medendorp S. Low-dose (7.5mg) oral methotrexate reduces the rate if progression in chronic progressive multiple sclerosis. Ann Neurol 1995; 37: 30-40.
95. Edan G, Miller D, Clanet M, et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicenter study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 1997; 62: 112-118.
96. Weiner HL, Dau PC, Khatri BO, et al. Double-blind study of true vs. sham plasma exchange in patients treated with immunosuppression for acute attacks of multiple sclerosis. Neurology 1989; 39: 1143-1149.
97. Rodriguez M, Karnes WE, Bartleson JD, Pineda AA. Plasmpheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology 1993; 43: 1100-1104.
98. Cook SD, Devereux C, Troiano R, et al. Total lymphoid irradiation in multiple sclerosis. In: Rudick RA, Goodkin DE, eds. Treatment of multiple sclerosis: trial design, results, and future perspectives. New York: Springer-Verlag, 1992: 267-280.