Multiple sclerosis: MHC associations and therapeutic implications

Expert Reviews in Molecular Medicine

Volumn 7, Issue 3, 2005, Pages

  Holmes, Samantha ^a   Friese, Manuel A ^b   Siebold, Christian ^a   Jones, E Yvonne ^a   Bell, John ^c   Fugger, Lars ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Antigen specific therapy; Autoimmunity; MHC; Multiple sclerosis; Structure; T cell receptor; TCR

Indexed keywords

ALEMTUZUMAB; ALPHA1 INTERFERON; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIHISTAMINIC AGENT; BETA INTERFERON; DACLIZUMAB; GLATIRIMER ACETATE; HLA DR2 ANTIGEN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IDEC C2B; IMMUNOMODULATING AGENT; IR 208; MITOXANTRONE; NATALIZUMAB; NEUROVAX; RITUXIMAB; T LYMPHOCYTE RECEPTOR; T LYMPHOCYTE RECEPTOR PEPTIDE; TM 27; UNCLASSIFIED DRUG; AUTOANTIGEN; IMMUNOLOGIC FACTOR; IMMUNOSUPPRESSIVE AGENT; LYMPHOCYTE ANTIGEN RECEPTOR;

ALLELE; ALLERGY; CLINICAL TRIAL; DRUG MECHANISM; GENE DISRUPTION; GENETIC ANALYSIS; GENETIC PREDISPOSITION; HAPLOTYPE; HUMAN; IMMUNE SYSTEM; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOTHERAPY; MAJOR HISTOCOMPATIBILITY COMPLEX; MOLECULAR BIOLOGY; MULTIPLE SCLEROSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN STRUCTURE; REVIEW; RISK ASSESSMENT; STRUCTURE ANALYSIS; T LYMPHOCYTE; ANIMAL; CD4+ T LYMPHOCYTE; DISEASE MODEL; GENETICS; IMMUNOLOGY; LEUKAPHERESIS; MOLECULAR MIMICRY; MOUSE; TRANSGENIC MOUSE;

ANIMALS; AUTOANTIGENS; CD4-POSITIVE T-LYMPHOCYTES; DISEASE MODELS, ANIMAL; GENETIC PREDISPOSITION TO DISEASE; HAPLOTYPES; HLA-DR2 ANTIGEN; HUMANS; IMMUNOLOGIC FACTORS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; LEUKOCYTE REDUCTION PROCEDURES; MAJOR HISTOCOMPATIBILITY COMPLEX; MICE; MICE, TRANSGENIC; MOLECULAR MIMICRY; MULTIPLE SCLEROSIS; RECEPTORS, ANTIGEN, T-CELL;

EID: 31044443332     PISSN: 14623994     EISSN: None     Source Type: Journal    
DOI: 10.1017/S1462399405008914     Document Type: Review

References (126)

1. Noseworthy, J.H. et al. (2000) Multiple sclerosis. N Engl J Med 343, 938-952,
2. Steinman, L. (2001) Multiple sclerosis: a two-stage disease. Nat Immunol 2, 762-764,
3. Hauser, S.L. et al. (1986) Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions. Ann Neurol 19, 578-587,
4. Hohlfeld, R. and Wekerle, H. (2001) Immunological update on multiple sclerosis. Curr Opin Neurol 14, 299-304,
5. Traugott, U., Reinherz, E.L. and Raine, C.S. (1983) Multiple sclerosis. Distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of Different ages. J Neuroimmunol 4, 201-221,
6. Hemmer, B., Archelos, J.J. and Hartung, H.P. (2002) New concepts in the immunopathogenesis of multiple sclerosis. Nat Rev Neurosci 3, 291-301,
7. Steinman, L. (1996) Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system. Cell 85, 299-302,
8. Martin, R., Sturzebecher, C.S. and McFarland, H.F. (2001) Immunotherapy of multiple sclerosis: where are we? Where should we go? Nat Immunol 2, 785-788,
9. Nepom, G.T. and Erlich, H. (1991) MHC class-II molecules and autoimmunity. Annu Rev Immunol 9, 493-525,
10. Stastny, P. (1978) Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 298, 869-871,
11. Sollid, L.M. et al. (1989) Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. J Exp Med 169, 345-350,
12. Sollid, L.M. and Thorsby, E. (1993) HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis. Gastroenterology 105, 910-922,
13. Ebers, G.C., Sadovnick, A.D. and Risch, N.J. (1995) A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 377, 150-151,
14. Oksenberg, J.R. et al. (1993) Genetic factors in multiple sclerosis. Jama 270, 2362-2369,
15. Oksenberg, J.R. et al. (1993) Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature 362, 68-70,
16. Altmann, D.M., Sansom, D. and Marsh, S.G. (1991) What is the basis for HLA-DQ associations with autoimmune disease? Immunol Today 12, 267-270,
17. Barcellos, L.F. et al. (2003) HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course. Am J Hum Genet 72, 710-716,
18. Celius, E.G. et al. (2000) Sex and age at diagnosis are correlated with the HLA-DR2, DQ6 haplotype in multiple sclerosis. J Neurol Sci 178, 132-135,
19. Hensiek, A.E. et al. (2002) HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis. J Neurol Neurosurg Psychiatry 72, 184-187,
20. Oksenberg, J.R. et al. (2004) Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans. Am J Hum Genet 74, 160-167,
21. Caballero, A. et al. (1999) DQB1*0602 confers genetic susceptibility to multiple sclerosis in Afro-Brazilians. Tissue Antigens 54, 524-526,
22. Serjeantson, S.W. et al. (1992) Novel HLA-DR2-related haplotypes in Hong Kong Chinese implicate the DQB1*0602 allele in susceptibility to multiple sclerosis. Eur J Immunogenet 19, 11-19,
23. Spurkland, A. et al. (1997) The HLA-DQ(alpha 1*0102, beta 1*0602) heterodimer may confer susceptibility to multiple sclerosis in the absence of the HLA-DR(alpha 1*01, beta 1*1501) heterodimer. Tissue Antigens 50, 15-22,
24. Marrosu, M.G. et al. (1997) Multiple sclerosis in Sardinia is associated and in linkage disequilibrium with HLA-DR3 and -DR4 alleles. Am J Hum Genet 61, 454-457,
25. Marrosu, M.G. et al. (2001) Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia. Hum Mol Genet 10, 2907-2916,
26. Ebers, G.C. et al. (1996) A full genome search in multiple sclerosis. Nat Genet 13, 472-476,
27. Rubio, J.P. et al. (2002) Genetic dissection of the human leukocyte antigen region by use of haplotypes of Tasmanians with multiple sclerosis. Am J Hum Genet 70, 1125-1137,
28. Fogdell-Hahn, A. et al. (2000) Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. Tissue Antigens 55, 140-148,
29. Harbo H.F. et al. (2004) Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis. Tissue Antigens 63, 237-247,
30. Oldstone, M.B. (1987) Molecular mimicry and autoimmune disease. Cell 50, 819-820,
31. Pette, M. et al. (1990) Myelin autoreactivity in multiple sclerosis: recognition of myelin basic protein in the context of HLA-DR2 products by T lymphocytes of multiple-sclerosis patients and healthy donors. Proc Natl Acad Sci U S A 87, 7968-7972,
32. Noseworthy, J.H. (1999) Progress in determining the causes and treatment of multiple sclerosis. Nature 399, A40-47,
33. Kerlero de Rosbo, N. et al. (1993) Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein. J Clin Invest 92, 2602-2608,
34. Hellings, N. et al. (2001) T-cell reactivity to multiple myelin antigens in multiple sclerosis patients and healthy controls. J Neurosci Res 63, 290-302,
35. Allegretta, M. et al. (1990) T cells responsive to myelin basic protein in patients with multiple sclerosis. Science 247, 718-721,
36. Trotter, J.L. et al. (1991) Peripheral blood mononuclear cells from multiple sclerosis patients recognize myelin proteolipid protein and selected peptides. J Neuroimmunol 33, 55-62,
37. Wucherpfennig, K.W. et al. (1994) Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. J Exp Med 179, 279-290,
38. Smith, K.J. et al. (1998) Crystal structure of HLA-DR2 (DRA*0101, DRB1*1501) complexed with a peptide from human myelin basic protein. J Exp Med 188, 1511-1520,
39. Madsen, L.S. et al. (1999) A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat Genet 23, 343-347,
40. Krogsgaard, M. et al. (2000) Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85-99 complex. J Exp Med 191, 1395-1412,
41. Willer, C.J. and Ebers, G.C. (2000) Susceptibility to multiple sclerosis: interplay between genes and environment. Curr Opin Neurol 13, 241-247,
42. Lang, H.L. et al. (2002) A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol 3, 940-943,
43. Fogdell, A. et al. (1995) The multiple sclerosis- and narcolepsy-associated HLA class II haplotype includes the DRB5*0101 allele. Tissue Antigens 46, 333-336,
44. Mycko, M.P. et al. (2004) Cross-reactive TCR responses to self antigens presented by different MHC class II molecules. J Immunol 173, 1689-1698,
45. Jersild, C. et al. (1993) Multiple sclerosis in the Faroe Islands. VI. Studies of HLA markers. Tissue Antigens 42, 105-110,
46. Muraro, P.A. et al. (1997) Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire. J Clin Invest 100, 339-349,
47. Hausmann, S. et al. (1999) Structural features of autoreactive TCR that determine the degree of degeneracy in peptide recognition. J Immunol 162, 338-344,
48. Trotter, J.L. et al. (1998) T cell recognition of myelin proteolipid protein and myelin proteolipid protein peptides in the peripheral blood of multiple sclerosis and control subjects. J Neuroimmunol 84, 172-178,
49. Ohashi, T. et al. (1995) Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95-116 as an HLA-DR2, w15-associated determinant. Int Immunol 7, 1771-1778,
50. Kawamura, K. et al. (2000) Hla-DR2-restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice. J Clin Invest 105, 977-984,
51. Marrosu, M.G. et al. (1988) Sardinian multiple sclerosis is associated with HLA-DR4: a serologic and molecular analysis. Neurology 38, 1749-1753,
52. Grasso, M.G. et al. (1992) HLA determinants in familial multiple sclerosis. Neuroepidemiology 11, 85-89,
53. Victoria-Gutierrez, M. et al. (1991) DNA analysis of HLA-DR4B1 subtypes in multiple sclerosis by specific oligonucleotide probes. J Neuroimmunol 32, 279-283,
54. Quandt, J.A. et al. (2004) Unique clinical and pathological features in HLA-DRB1*0401-restricted MBP 111-129-specific humanized TCR transgenic mice. J Exp Med 200, 223-234,
55. De Pauw, A. et al. (2002) Dysphagia in multiple sclerosis. Clin Neurol Neurosurg 104, 345-351,
56. Hartelius, L. and Svensson, P. (1994) Speech and swallowing symptoms associated with Parkinson's disease and multiple sclerosis: a survey. Folia Phoniatr Logop 46, 9-17,
57. Thomas, F.J. and Wiles, C.M. (1999) Dysphagia and nutritional status in multiple sclerosis. J Neurol 246, 677-682,
58. Bettelli, E. et al. (2003) Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J Exp Med 197, 1073-1081,
59. Steinman, L. (2003) Optic neuritis, a new variant of experimental encephalomyelitis, a durable model for all seasons, now in its seventieth year. J Exp Med 197, 1065-1071,
60. Gregersen, J.W., Holmes, S. and Fugger, L. (2004) Humanized animal models for autoimmune diseases. Tissue Antigens 63, 383-394,
61. Yu, M. et al. (1996) Interferon-beta inhibits progression of relapsing-remitting experimental autoimmune encephalomyelitis. J Neuroimmunol 64, 91-100,
62. Hertz, F. and Deghenghi, R. (1985) Effect of rat and beta-human interferons on hyperacute experimental allergic encephalomyelitis in rats. Agents Actions 16, 397-403,
63. Teitelbaum, D. et al. (1971) Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur J Immunol 1, 242-248,
64. Aharoni, R., Teitelbaum, D. and Arnon, R. (1993) T suppressor hybridomas and interleukin-2-dependent lines induced by copolymer 1 or by spinal cord homogenate down-regulate experimental allergic encephalomyelitis. Eur J Immunol 23, 17-25,
65. Teitelbaum, D. et al. (1973) Suppression by several synthetic polypeptides of experimental allergic encephalomyelitis induced in guinea pigs and rabbits with bovine and human basic encephalitogen. Eur J Immunol 3, 273-279,
66. Teitelbaum, D. et al. (1974) Suppression of experimental allergic encephalomyelitis in Rhesus monkeys by a synthetic basic copolymer. Clin Immunol Immunopathol 3, 256-262,
67. Jacobs, L.D. et al. (1996) Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Ann Neurol 39, 285-294,
68. Jacobs, L.D. et al. (1993) Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. Neurology 43, 655-661,
69. Jacobs, L.D. et al. (1998) Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 352, 1498-1504,
70. Jacobs, L.D. et al. (1999) Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS Study. The Once Weekly Interferon for MS Study Group. Neurology 53, 679-686,
71. Johnson, K.P. et al. (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, 1268-1276,
72. Johnson, K.P. et al. (1998) Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group. Neurology 50, 701-708,
73. Bornstein, M.B. et al. (1987) A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N Engl J Med 317, 408-414,
74. Sela, M. (1999) The concept of specific immune treatment against autoimmune diseases. Int Rev Immunol 18, 201-216,
75. Comi, G. et al. (2001) Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357, 1576-1582,
76. Steinman, L. (2004) Immune therapy for autoimmune diseases. Science 305, 212-216,
77. Stuve, O. et al. (1996) Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9. Ann Neurol 40, 853-863,
78. Tuohy, V.K. et al. (1999) Spontaneous regression of primary autoreactivity during chronic progression of experimental autoimmune encephalomyelitis and multiple sclerosis. J Exp Med 189, 1033-1042,
79. Robinson, W.H. et al. (2003) Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. Nat Biotechnol 21, 1033-1039,
80. Fridkis-Hareli, M. and Strominger, J.L. (1998) Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules. J Immunol 160, 4386-4397,
81. Stern, J.N. et al. (2004) Amelioration of proteolipid protein 139-151-induced encephalomyelitis in SJL mice by modified amino acid copolymers and their mechanisms. Proc Natl Acad Sci U S A 101, 11743-11748,
82. Teitelbaum, D. et al. (1996) Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLP-specific T cell responses. J Neuroimmunol 64, 209-217,
83. Fridkis-Hareli, M. et al. (2002) Novel synthetic amino acid copolymers that inhibit autoantigen-specific T cell responses and suppress experimental autoimmune encephalomyelitis. J Clin Invest 109, 1635-1643,
84. Illes, Z. et al. (2004) Modified amino acid copolymers suppress myelin basic protein 85-99-induced encephalomyelitis in humanized mice through different effects on T cells. Proc Natl Acad Sci U S A 101, 11749-11754,
85. Chen, Y. et al. (1994) Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265, 1237-1240,
86. Weiner, H.L. (1997) Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 18, 335-343,
87. Karin, N. et al. (1994) Reversal of experimental autoimmune encephalomyelitis by a soluble peptide variant of a myelin basic protein epritope: T cell receptor antagonism and reduction of interferon gamma and tumor necrosis factor alpha production. J Exp Med 180, 2227-2237,
88. Brocke, S. et al. (1996) Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein. Nature 379, 343-346,
89. Bielekova, B. et al. (2000) 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 6, 1167-1175,
90. Kappos, L. et al. (2000) 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. The Altered Peptide Ligand in Relapsing MS Study Group. Nat Med 6, 1176-1182,
91. Vandenbark, A.A. et al. (2003) Recombinant TCR ligand induces tolerance to myelin oligodendrocyte glycoprotein 35-55 peptide and reverses clinical and histological signs of chronic experimental autoimmune encephalomyelitis in HLA-DR2 transgenic mice. J Immunol 171, 127-133,
92. Burrows, G.G. et al. (2000) Regulation of encephalitogenic T cells with recombinant TCR ligands. J Immunol 164, 6366-6371,
93. Burrows, G.G. et al. (1998) Two-domain MHC class II molecules form stable complexes with myelin basic protein 69-89 peptide that detect and inhibit rat encephalitogenic T cells and treat experimental autoimmune encephalomyelitis. J Immunol 161, 5987-5996,
94. Aharoni, R. et al. (1991) Immunomodulation of experimental allergic encephalomyelitis by antibodies to the antigen-Ia complex. Nature 351, 147-150,
95. Shaw, M.K. et al. (1997) Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis. J Exp Med 185, 1711-1714,
96. Costal G.L. et al. (2001) Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit. J Immunol 167, 2379-2387,
97. Kotzin, B.L. et al. (1991) Preferential T-cell receptor beta-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis. Proc Natl Acad Sci U S A 88, 9161-9165,
98. Musette, P. et al. (1996) Expansion of a recurrent V beta 5.3+ T-cell population in newly diagnosed and untreated HLA-DR2 multiple sclerosis patients. Proc Natl Acad Sci U S A 93, 12461-12466,
99. Lozeron, P. et al. (1998) T cell receptor V beta 5 and V beta 17 clonal diversity in cerebrospinal fluid and peripheral blood lymphocytes of multiple sclerosis patients. Mult Scler 4, 154-161,
100. Killestein, J. et al. (2002) Antibody-mediated suppression of Vbeta5.2/ 5.3(+) T cells in multiple sclerosis: results from an MRI-monitored phase II clinical trial. Ann Neurol 51, 467-474,
101. Olsson, T. et al. (2002) Depletion of Vbeta5.2/5.3 T cells with a humanized antibody in patients with multiple sclerosis. Eur J Neurol 9, 153-164,
102. Medaer, R. et al. (1995) Depletion of myelin-basic-protein autoreactive T cells by T-cell vaccination: pilot trial in multiple sclerosis. Lancet 346, 807-808,
103. Van der Aa, A. et al. (2003) T cell vaccination in multiple sclerosis patients with autologous CSF-derived activated T cells: results from a pilot study. Clin Exp Immunol 131, 155-168,
104. Achiron, A. et al. (2004) T cell vaccination in multiple sclerosis relapsing-remitting nonresponders patients. Clin Immunol 113, 155-160,
105. Rose, J.W. et al. (2004) Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol 56, 864-867,
106. Nussenblatt, R.B. et al. (2003) Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration. J Autoimmun 21, 283-293,
107. Paolillo, A. et al. (1999) Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H. Neurology 53, 751-757,
108. Coles, A., Deans, J. and Compston, A. (2004) Campath-1H treatment of multiple sclerosis: lessons from the bedside for the bench. Clin Neurol Neurosurg 106, 270-274,
109. Coles, A.J. et al. (1999) Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 354, 1691-1695,
110. Miller, D.H. et al. (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348, 15-23,
111. Yednock, T.A. et al. (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356, 63-66,
112. Shenkenberg, T.D. and Von Hoff, D.D. (1986) Mitoxantrone: a new anticancer drug with significant clinical activity. Ann Intern Med 105, 67-81,
113. Assanasen, P. and Naclerio, R.M. (2002) Antiallergic anti-inflammatory effects of H1-antihistamines in humans. Clin Allergy Immunol 17, 101-139,
114. Chiong, J.R. and Miller, A.B. (2002) Reninangiotensin system antagonism and lipid-lowering therapy in cardiovascular risk management. J Renin Angiotensin Aldosterone Syst 3, 96-102,
115. Rosenson, R.S. (2004) Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities. Atherosclerosis 173, 1-12,
116. Duval, C. et al. (2002) The role of PPARs in atherosclerosis. Trends Mol Med 8, 422-430,
117. Edan, G. et al. (1997) Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 62, 112-118,
118. Hartung, H.P. et al. (2002) Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 360, 2018-2025,
119. Neuhaus, O. et al. (2002) Multiple Sclerosis: immunological effects of mitoxantrone in vitro reveal antigen-presenting cells as major targets. Eur J Neurol 9, 130
120. Polman, C.H. and Uitdehaag, B.M. (2003) New and emerging treatment options for multiple sclerosis. Lancet Neurol 2, 563-566,
121. Youssef, S. et al. (2002) The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420, 78-84,
122. Lovett-Racke, A.E. et al. (2004) Peroxisome proliferator-activated receptor alpha agonists as therapy for autoimmune disease. J Immunol 172, 5790-5798,
123. Constantinescu, C.S. et al. (1995) Effects of the angiotensin converting enzyme inhibitor captopril on experimental autoimmune encephalomyelitis. Immunopharmacol Immunotoxicol 17, 471-491,
124. Pedotti, R. et al. (2003) Involvement of both 'allergic' and 'autoimmune' mechanisms in EAE, MS and other autoimmune diseases. Trends Immunol 24, 479-484,
125. Vollmer, T. et al. (2004) Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363, 1607-1608,
126. Wiendl, H. et al. (2004) [Multiple sclerosis: potential therapeutic options and update of ongoing studies]. Nervenarzt 75, 536-552,