Abstract
Ten chapters of this book are devoted to specific therapeutic strategies for multiple sclerosis (MS). It will be immediately noted that all of these strategies involve manipulation of the patient’s immune system. These immune-modulatory strategies comprise a broad spectrum. At one end are the global immunosuppressives, both anti-inflammatory (corticosteroids), cytotoxic (azathioprine, cyclophosphamide), and total lymphoid irradiation and plasmapheresis. Slightly more specific immune modulators include cyclosporine A and anti-T cell antibodies. The rationale for using interferons to treat MS relies primarily on their immunoregulatory potential although antiviral effects may also be desirable. Finally, several elegant strategies for specific immunotherapy directed against small numbers of presumed pathogenic immunocompetent cells are also described. If the majority of effort in studying experimental therapies for MS is directed at manipulating the immune system, then the task of explaining the rationale for this approach reduces to explaining why MS is thought to be an immune-mediated disorder. In this chapter, the concept of MS immunopathogenesis will be reviewed, with concentration primarily on the epidemiologic data and derivative clinical investigations. Where possible, references are to reviews, to facilitate further reading.
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Keywords
- Multiple Sclerosis
- Multiple Sclerosis Patient
- Myelin Basic Protein
- Progressive Multifocal Leukoencephalopathy
- Demyelinating Disease
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.
References
Acheson E (1985) The epidemiology of multiple sclerosis. In: Matthews W, Batchelor J, Acheson E, Weller R (eds) McAlpine’s multiple sclerosis. Churchill Livingstone, Edinburgh, pp 3–46
Adams C (1983) The general pathology of multiple sclerosis: morphological and chemical aspects of the lesions. In: Hallpike J, Adams C, Tourtellotte W (eds) Multiple sclerosis: pathology, diagnosis and management. Chapman and Hall, London, pp 203–240
Allegretta M, Nicklas JA, Siram S, Albertini RJ (1990) T cells responsive to myelin basic protein in patients with multiple sclerosis. Science 247: 718–721
Bangham C, Nightingale S, Cruickshank J, Daenke S (1989) PCR analysis of DNA from multiple sclerosis patients for the presence of HTLV-I. Science 246: 821
Batchelor J (1985) The immunological and genetic aspects of multiple sclerosis. In: Matthews W, Batchelor J, Acheson E, Weller R (eds) McAlpine’s multiple sclerosis. Churchill Livingstone, Edinburgh, pp 479–513
Beall S, Concannon P, Charmely P, McFarland H, Gatti R, Hood L, McFarlin D, Biddison W (1989) The germline repertoire of T-cell receptor ĂŸ-chain genes in patients with chronic progressive multiple sclerosis. J Neuroimmunol 21: 59–66
Brew B, Price R (1988) Another retroviral disease of the nervous system: chronic progressive myelopathy due to HTLV-I. N Engl J Med 318: 1195–1197
Ebers G, Bulman D, Sadovnick A (1986) A population based study of multiple sclerosis in twins. N Engl J Med 315: 1638–1642
Hafler DA, Duby AD, Lee SJ, Benjamin D, Seidman JG, Weiner HL (1988) Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 167: 1313–1322
Hayashi T, Morimoto C, Burks J, Kerr C, Hauser SL (1988) Dual-label immunocytochemistry of the active multiple sclerosis lesion: major histocompatibility complex and activation antigens. Ann Neurol 24: 523–531
Hofman FM, von Hanwehr RI, Dinarello CA, Mizel SB, Hinton D, Merrill JE (1986) Immunoregulatory molecules and IL-2 receptors identified in multiple sclerosis brain. J Immunol 136: 3239–3247
Hofman FM, Hinton DR, Johnson K, Merrill JE (1989) Tumor necrosis factor identified in multiple sclerosis brain. J Exp Med 170: 607–612
Jacobsen S, Raine C, Mingioloi E, McFarlin D (1988) Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis. Nature 331: 540–543
Jersild C, Svejgard A, Fog T (1972) HLA antigens and multiple sclerosis. Lancet 1: 1240–1241
Johnson R (1982) Viral infections of the nervous system. Raven, New York
Johnson R (1983) Persistent viral infections and demyelinating diseases: an overview. In: Mims C, Cuzner M, Kelly R (eds) Viruses and demyelinating diseases. Academic Press, London, pp 7–20
Johnson R, McArthur J (1987) Myelopathies and retroviral infections. Ann Neurol 21: 113–116
Kinnunen E, Koskenvuo M, Kaprio J, Aho K (1987) Multiple sclerosis in a nationwide series of twins. Neurology 37: 1627–1629
Knobler R, Oldstone M (1983) The role of host genes and virus-cell tropism in coronavirusinduced demyelination: a unique murine experimental model for understanding human demyelinating disease. In: Mims C, Cuzner M, Kelly R (eds) Viruses and demyelinating disease’s. Academic Press, London, pp 53–66
Kurtzke J (1983) Fine structure of the demyelinating process. In: Hallpike J, Adams C, Tourtellotte W (eds) Multiple sclerosis: pathology, diagnosis and management. Chapman and Hall, London, pp 47–96
Lampert P (1983) Fine structure of the demyelinating process. In: Hallpike J, Adams C, Tourtellotte W (eds) Multiple sclerosis: pathology, diagnosis and management. Chapman and Hall, London, pp 29–46
Lassmann H (1983) Comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis. Springer Verlag, Berlin
Leibowitz S (1983) The immunology of multiple sclerosis. In: Hallpike J, Adams C, Tourtellotte W (eds) Multiple sclerosis: pathology, diagnosis and management. Chapman and Hall, London, pp 379–412
McFarlin D, Lachman P (1989) Hopeful genes and immunology. Nature 341: 693–694
Merritt H (1970) Multiple sclerosis: a clinical science review. Med World News, July 24
Narayan O, Strandberg J, Griffin D, Clements J, Adams R (1983) Aspects of the pathogenesis of Visna in sheep. In: Mims C, Cuzner M, Kelly R (eds) Viruses and demyelinating diseases. Academic Press, London, pp 125–140
Reddy E (1989) PCR analysis of DNA from multiple sclerosis patients for the presence of HTLV-I. Science 246: 823–824
Richardson J, Wucherpfennig K, Endo N, Rudge P, Dalgleish A, Hafler D (1989) PCR analysis of DNA from multiple sclerosis patients for presence of HTLV-I. Science 246: 821–823
Rodriguez M, Oleszak E, Leibowitz J (1987) Theiler’s murine encephalomyelitis: a model of demyelination and persistence of virus. CRC Crit Rev Immunol 7: 325–365
Salmi A, Arnadottir T, Reunanen M, Ilonen J (1983) The significance of viral antibody synthesis in the central nervous system of multiple sclerosis patients In Mims C, Cuzner M, Kelly R (eds) Viruses and demyelinating diseases. Academic Press, London, pp 141–152
Scheinberg L, Korey S (1962) Multiple sclerosis. Annu Rev Med 13: 411–430
Seboun E, Robinson M, Doolittle T, Ciulla T, Kindt T, Hauser S (1989) A susceptibility locus for multiple sclerosis is linked to the T cell ĂŸ chain complex. Cell 57: 1095–1100
Sobel RA (1989) T-lymphocyte subsets in the multiple sclerosis lesion. Res Immunol 140: 208–211
Sobel RA, Hafler DA, Castro EE, Morimoto C, Weiner HL (1988) The 2H4 (CD45R) antigen is selectively decreased in multiple sclerosis lesions. J Immunol 140: 2210–2214
Stein EC, Schiffer RB, Hall WJ, Young N (1987) Multiple sclerosis and the workplace: Report of an industry-based cluster. Neurology 37: 1672–1677
Stewart, G, Kirk R (1983) The genetics of multiple sclerosis: the HLA system and other demyelinating diseases. In: Hallpike J, Adams C, Tourtellotte W (eds) Multiple sclerosis: pathology, diagnosis and management. Chapman and Hall, London, pp 241–274
ter Meulen V, Stephenson J (1983) The possible role of viral infections in multiple sclerosis and other genetic markers. In: Hallpike J, Adams C, Tourtellotte W (eds) Multiple sclerosis: pathology, diagnosis and management. Chapman and Hall, London, pp 241–274
Traugott U (1987) Multiple sclerosis: relevance of class I and class II MHC-expressing cells to lesion development. J Neuroimmunol 16: 283–302
Traugott U, Lebon P (1988a) Demonstration of alpha, beta, and gamma interferon in active chronic multiple sclerosis lesions. Ann NY Acad Sci 540: 309–311
Traugott U, Lebon P (1988b) Interferon-gamma and la antigen are present on astrocytes in active chronic multiple sclerosis lesions. J Neurol Sci 84: 257–264
Traugott U, Reinherz E, Raine C (1983) Multiple sclerosis: distribution of T-cell subsets within active chronic lesions. Science 219: 308–310
Vartdal F (1989) HLA association in multiple sclerosis: implications for immunopathogenesis. Res Immunol 140: 192–196
Waksman B (1983) Viruses and immune events in the pathogenesis of multiple sclerosis. In: Mims C, Cuzner M, Kelly’ R (eds) Viruses and demyelinating diseases. Academic Press, London, pp 155–166
Waksman B (1989) Multiple sclerosis: relationship to a retrovirus? Nature 337: 599
Walsh M, Tourtellotte W (1983) The cerebrospinal fluid in multiple sclerosis. In: Hallpike J, Adams C, Tourtellotte W (eds) Multiple sclerosis: pathology, diagnosis and management. Chapman and Hall, London, pp 275–358
Weller R (1985) Experimental demyelinating diseases and their relevance to multiple sclerosis. In: Matthews W, Batchelor J, Acheson E, Weller R (eds) McAlpine’s multiple sclerosis. Churchill Livingstone, Edinburgh, pp 344–348
Wolf A (1952) A review of experimental studies on the etiology of the human demyelinating diseases. In: The First International Congress of Neuropathology. Tipografia G. Dommini, Rome, pp 1–60
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Ransohoff, R.M. (1992). Pathogenesis of Multiple Sclerosis: Relationship to Therapeutic Strategies. In: Rudick, R.A., Goodkin, D.E. (eds) Treatment of Multiple Sclerosis. Clinical Medicine and the Nervous System. Springer, London. https://doi.org/10.1007/978-1-4471-3184-7_5
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