Pathogenic mechanisms and experimental models of multiple sclerosis

Autoimmunity

Volumn 43, Issue 7, 2010, Pages 504-513

  Slavin, Anthony ^a   Kelly Modis, Louise ^a   Labadia, Mark ^a   Ryan, Kelli ^a   Brown, Maryanne L ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

autoimmune disease; experimental encephalomyelitis; Multiple sclerosis

Indexed keywords

ALEMTUZUMAB; BETA1A INTERFERON; BIOLOGICAL MARKER; CLADRIBINE; CYCLOPHOSPHAMIDE; DACLIZUMAB; FINGOLIMOD; GLATIRAMER; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERFERON; INTERFERON BETA SERINE; LAQUINIMOD; NATALIZUMAB; RITUXIMAB; ROQUINIMEX; SALAZOSULFAPYRIDINE; TERIFLUNOMIDE; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; USTEKINUMAB;

ALLERGIC ENCEPHALOMYELITIS; ANTIGEN PRESENTING CELL; AUTOIMMUNITY; B LYMPHOCYTE; BRADYCARDIA; CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; CELL TYPE; CLINICAL EFFECTIVENESS; CROHN DISEASE; DISEASE SEVERITY; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DYSPNEA; GENE EXPRESSION; GENE MUTATION; GENETIC SUSCEPTIBILITY; HUMAN; INFECTION; LEUKOCYTE; LEUKOENCEPHALOPATHY; LIVER INJURY; LYMPHOCYTOPENIA; MELANOMA; MULTIPLE SCLEROSIS; MYELODYSPLASTIC SYNDROME; NONHUMAN; PATHOGENESIS; RETINA MACULA EDEMA; REVIEW; RHINOPHARYNGITIS; SIDE EFFECT; SINGLE DRUG DOSE; THROMBOCYTOPENIC PURPURA; UNSPECIFIED SIDE EFFECT;

ANIMALS; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; GENETIC PREDISPOSITION TO DISEASE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; IMMUNOTHERAPY; MULTIPLE SCLEROSIS;

EID: 77958006059     PISSN: 08916934     EISSN: 1607842X     Source Type: Journal    
DOI: 10.3109/08916931003674733     Document Type: Review

References (75)

1. Hauser SL. Multiple lessons for multiple sclerosis. N Engl J Med 2008;359(17):1838-1841.
2. Compston A. McAlpine's multiple sclerosis. 4th ed. Philadelphia: Churchill Livingstone Elsevier; 2006.
3. Sotgiu S, Pugliatti M, Fois ML, Arru G, Sanna A, Sotgiu MA, Rosati G. Genes, environment, and susceptibility to multiple sclerosis. Neurobiol Dis 2004;17(2):131-143.
4. Fugger L, Friese MA, Bell JI. From genes to function: The next challenge to understanding multiple sclerosis. Nat Rev Immunol 2009;9(6):408-417.
5. Frohman EM, Racke MK, Raine CS. Multiple sclerosis\-the plaque and its pathogenesis. N Engl J Med 2006;354(9): 942-955.
6. Geurts JJ, Barkhof F. Grey matter pathology in multiple sclerosis. Lancet Neurol 2008;7(9):841-851.
7. Weiner HL. The challenge of multiple sclerosis: How do we cure a chronic heterogeneous disease? Ann Neurol 2009; 65(3):239-248.
8. Wiendl H, Hohlfeld R. Therapeutic approaches in multiple sclerosis: Lessons from failed and interrupted treatment trials. BioDrugs 2002;16(3):183-200.
9. Clerico M, Contessa G, Durelli L. Interferon-beta1a for the treatment of multiple sclerosis. Expert Opin Biol Ther 2007; 7(4):535-542.
10. Arnon R, Aharoni R. Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications. Proc Natl Acad Sci USA 2004;101(Suppl. 2):14593-14598.
11. Vandenbark AA, Huan J, Agotsch M, La TD, Goelz S, Offner H, Lanker S, Bourdette D. Interferon-beta-1a treatment increases CD56bright natural killer cells and CD4\+ CD25\+ Foxp3 expression in subjects with multiple sclerosis. J Neuroimmunol 2009;215(1-2):125-128.
12. Comi G, Martinelli V, Rodegher M, Moiola L, Bajenaru O, Carra A, Elovaara I, Fazekas F, Hartung HP, Hillert J, King J, Komoly S, Lubetzki C, Montalban X, Myhr KM, Ravnborg M, Rieckmann P, Wynn D, Young C, Filippi M. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): A randomised, double-blind, placebo-controlled trial. Lancet 2009;374(9700):1503-1511.
13. Haas J, Korporal M, Balint B, Fritzsching B, Schwarz A, Wildemann B. Glatiramer acetate improves regulatory T-cell function by expansion ofnaive CD4(\+)CD25(\+)FOXP3(\+)-CD31(\+) T-cells in patients with multiple sclerosis. J Neuroimmunol 2009;216(1-2):113-117.
14. Yang JS, Xu LY, Xiao BG, Hedlund G, Link H. Laquinimod (ABR-215062) suppresses the development of experimental autoimmune encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF-beta in Lewis rats. J Neuroimmunol 2004;156(1-2):3-9.
15. Warnke C, Meyer Zu HG, Hartung HP, Stuve O, Kieseier BC. Review of teriflunomide and its potential in the treatment of multiple sclerosis. Neuropsychiatr Dis Treat 2009;5:333-340.
16. Linker RA, Kieseier BC, Gold R. Identification and development of new therapeutics for multiple sclerosis. Trends Pharmacol Sci 2008;29(11):558-565.
17. O'Connor P, Comi G, Montalban X, Antel J, Radue EW, de VA, Pohlmann H, Kappos L. Oral fingolimod (FTY720) in multiple sclerosis: Two-year results of a phase II extension study. Neurology 2009;72(1):73-79.
18. Sawicka E, Dubois G, Jarai G, Edwards M, Thomas M, Nicholls A, Albert R, Newson C, Brinkmann V, Walker C. The sphingosine 1-phosphate receptor agonist FTY720 differentially affects the sequestration of CD4\+/CD25\+ T-regulatory cells and enhances their functional activity. J Immunol 2005;175(12):7973-7980.
19. Osborne R. Buzz around Campath proof-of-concept trial in MS. Nat Biotechnol 2009;27(1):6-8.
20. Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon b-1a in early multiple sclerosis. N Engl J Med 2008; 359(17):1786-1801.
21. Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol 2005;35(11):3332-3342.
22. Bielekova B,RichertN,HowardT,BlevinsG, Markovic-Plese S, McCartin J, Frank JA, Wurfel J, Ohayon J, Waldmann TA, McFarland HF, Martin R. Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proc Natl Acad Sci USA 2004; 101(23):8705-8708.
23. Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ra-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci USA 2006;103(15):5941- 5946.
24. Samijn JP, te Boekhorst PA, Mondria T, van Doorn PA, Flach HZ, van der Meche FG, Cornelissen J, Hop WC, Lowenberg B, Hintzen RQ. Intense T-cell depletion followed by autologous bone marrow transplantation for severe multiple sclerosis. J Neurol Neurosurg Psych 2006;77(1):46-50.
25. Krishnan C, Kaplin AI, Brodsky RA, Drachman DB, Jones RJ, Pham DL, Richert ND, Pardo CA,Yousem DM, Hammond E, Quigg M, Trecker C, McArthur JC, Nath A, Greenberg BM, Calabresi PA, Kerr DA. Reduction of disease activity and disability with high-dose cyclophosphamide in patients with aggressive multiple sclerosis. Arch Neurol 2008;65(8): 1044-1051.
26. Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358(7):676-688. (Pubitemid 351240747)
27. Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, SimonJ,HauserS,WaubantE, Vollmer T,PanitchH, Zhang J, Chin P, Smith CH. Rituximab in patients with PP multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 2009;66(4): 460-471.
28. Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: A phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008;7(9):796-804.
29. Martin R. Neutralisation of IL12 p40 or IL23 p40 does not block inflammation in multiple sclerosis. Lancet Neurol 2008; 7(9):765-766.
30. Kroenke MA, Carlson TJ, Andjelkovic AV, Segal BM. IL-12-and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J Exp Med 2008;205(7):1535-1541.
31. Steinman L, Zamvil SS. Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. Trends Immunol 2005;26(11):565-571.
32. Lincoln MR, Montpetit A, Cader MZ, Saarela J, Dyment DA, Tiislar M, Ferretti V, Tienari PJ, Sadovnick AD, Peltonen L, Ebers GC, Hudson TJ. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet 2005;37(10):1108-1112.
33. Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, de Bakker PI, Gabriel SB, Mirel DB, Ivinson AJ, Pericak-Vance MA, Gregory SG, Rioux JD, McCauley JL, Haines JL, Barcellos LF, Cree B, Oksenberg JR, Hauser SL. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007;357(9):851-862.
34. Weber F, Fontaine B, Cournu-Rebeix I, Kroner A, Knop M, Lutz S, Muller-Sarnowski F, Uhr M, Bettecken T, Kohli M, Ripke S, Ising M, Rieckmann P, Brassat D, Semana G, Babron MC, Mrejen S, Gout C, Lyon-Caen O, Yaouanq J, Edan G, Clanet M, Holsboer F, Clerget-Darpoux F, Muller-Myhsok B. IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations. Genes Immun 2008;9(3):259-263.
35. Lowe CE, Cooper JD, Brusko T, Walker NM, Smyth DJ, Bailey R, Bourget K, Plagnol V, Field S, Atkinson M, Clayton DG, Wicker LS, Todd JA. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet 2007;39(9):1074-1082.
36. [Anonymous]. The expanding genetic overlap between multiple sclerosis and type I diabetes. Genes Immun 2009; 10(1):11-14.
37. Hafler JP, Maier LM, Cooper JD, Plagnol V, Hinks A, Simmonds MJ, Stevens HE, Walker NM, Healy B, Howson JM, Maisuria M, Duley S, Coleman G, Gough SC, Worthington J, Kuchroo VK, Wicker LS, Todd JA. CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immun 2009;10(1):5-10.
38. Dardalhon V, Schubart AS, Reddy J, Meyers JH, Monney L, Sabatos CA, Ahuja R, Nguyen K, Freeman GJ, Greenfield EA, Sobel RA, Kuchroo VK. CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions. J Immunol 2005;175(3):1558-1565.
39. Zoledziewska M, Costa G, Pitzalis M, Cocco E, Melis C, Moi L, Zavattari P, Murru R, Lampis R, Morelli L, Poddie F, Frongia P, Pusceddu P, Bajorek M, Marras A, Satta AM, Chessa A, Pugliatti M, Sotgiu S, Whalen MB, Rosati G, Cucca F, Marrosu MG. Variation within the CLEC 16 A gene shows consistent disease association with both multiple sclerosis and type 1 diabetes in Sardinia. Genes Immun 2009;10(1):15-17.
40. Aulchenko YS, Hoppenbrouwers IA, Ramagopalan SV, Broer L, Jafari N, Hillert J, Link J, Lundstrom W, Greiner E, Dessa SA, Goossens D, Van BC, Del-Favero J, Ebers GC, Oostra BA, van Duijn CM, Hintzen RQ. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nat Genet 2008;40(12):1402-1403.
41. Ban M, Goris A, Lorentzen AR, Baker A, Mihalova T, Ingram G, Booth DR, Heard RN, Stewart GJ, Bogaert E, Dubois B, Harbo HF, Celius EG, Spurkland A, Strange R, Hawkins C, Robertson NP, Dudbridge F, Wason J, De Jager PL, Hafler D, Rioux JD, Ivinson AJ, McCauley JL, Pericak-Vance M, Oksenberg JR, Hauser SL, Sexton D, Haines J, Sawcer S, Compston A. Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. Eur J Hum Genet 2009;17(10):1309-1313.
42. De Jager PL, Jia X, Wang J, de Bakker PI, Ottoboni L, Aggarwal NT, Piccio L, Raychaudhuri S, Tran D, Aubin C, Briskin R, Romano S, Baranzini SE, McCauley JL, Pericak-Vance MA, Haines JL, Gibson RA, Naeglin Y, Uitdehaag B, Matthews PM, Kappos L, Polman C, McArdle WL, Strachan DP, Evans D, Cross AH, Daly MJ, Compston A, Sawcer SJ, Weiner HL, Hauser SL, Hafler DA, Oksenberg JR. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 2009;41(7):776-782.
43. Caillier S, Barcellos LF, Baranzini SE, Swerdlin A, Lincoln RR, Steinman L, Martin E, Haines JL, Pericak-Vance M, Hauser SL, Oksenberg JR. Osteopontin polymorphisms and disease course in multiple sclerosis. Genes Immun 2003; 4(4):312-315.
44. Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De JP, Baecher-Allan C. Multiple sclerosis. Immunol Rev 2005;204: 208-231.
45. Ransohoff RM, Kivisakk P, Kidd G. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 2003;3(7):569-581.
46. Lock C, Hermans G, Pedotti R, Brendolan A, Schadt E, Garren H, Langer-Gould A, Strober S, Cannella B, Allard J, Klonowski P, Austin A, Lad N, Kaminski N, Galli SJ, Oksenberg JR, Raine CS, Heller R, Steinman L. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002;8(5):500-508.
47. LiuX,Lee YS,YuCR, Egwuagu CE. LossofSTAT3 inCD4\+ T cells prevents development of experimental autoimmune diseases. J Immunol 2008;180(9):6070- 6076.
48. Haak S, Croxford AL, Kreymborg K, Heppner FL, Pouly S, Becher B, Waisman A. IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice. J Clin Invest 2009;119(1):61-69.
49. O'Connor RA, Prendergast CT, Sabatos CA, Lau CW, Leech MD, Wraith DC, Anderton SM. Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis. J Immunol 2008;181(6):3750-3754.
50. Stromnes IM, Cerretti LM, Liggitt D, Harris RA, Goverman JM. Differential regulation of central nervous system autoimmunity by Th1 and Th17 cells. Nat Med 2008; 14(3):337-342.
51. Eikelenboom MJ, Killestein J, Izeboud T, Kalkers NF, van Lier RA, Barkhof F, Uitdehaag BM, Polman CH. Chemokine receptor expression on T cells is related to new lesion development in multiple sclerosis. J Neuroimmunol 2002;133(1-2):225-232.
52. Blink SE, Miller SD. The contribution of gammadelta T cells to the pathogenesis of EAE and MS. Curr Mol Med 2009; 9(1):15-22.
53. Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity 2009;31(2): 331-341.
54. Franciotta D, Salvetti M, Lolli F, Serafini B, Aloisi F. B cells and multiple sclerosis. Lancet Neurol 2008;7(9):852-858.
55. Heppner FL, Greter M, Marino D, Falsig J, Raivich G, Hovelmeyer N, Waisman A, Rulicke T, Prinz M, Priller J, Becher B, Aguzzi A. Experimental autoimmune encephalo-myelitis repressed by microglial paralysis. Nat Med 2005; 11(2):146-152.
56. Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 2005;11(3):328-334.
57. Bailey-Bucktrout SL, Caulkins SC, Goings G, Fischer JA, Dzionek A, Miller SD. Cutting edge: Central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis. J Immunol 2008;180(10):6457-6461.
58. Bayas A, Stasiolek M, Kruse N, Toyka KV, Selmaj K, Gold R. Altered innate immune response of plasmacytoid dendritic cells in multiple sclerosis. Clin Exp Immunol 2009;157(3): 332-342.
59. Bailey SL, Schreiner B, McMahon EJ, Miller SD. CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4\+ Th-17 cells in relapsing EAE. Nat Immunol 2007;8(2):172-180.
60. Deshpande P, King IL, Segal BM. Cutting edge: CNS CD11c\+ cells from mice with encephalomyelitis polarize Th17 cells and support CD25\+CD4\+ T cell-mediated immunosuppression, suggesting dual roles in the disease process. J Immunol 2007;178(11):6695-6699.
61. Becher B, Durell BG, Miga AV, Hickey WF, Noelle RJ. The clinical course of experimental autoimmune encephalo-myelitis and inflammation is controlled by the expression of CD40 within the central nervous system. J Exp Med 2001; 193(8):967-974.
62. Weber F, Meinl E, Aloisi F, Nevinny-Stickel C, Albert E, Wekerle H, Hohlfeld R. Human astrocytes are only partially competent antigen presenting cells. Possible implications for lesion development in multiple sclerosis. Brain 1994; 117(Pt 1):59-69.
63. Stuve O, Youssef S, Slavin AJ, King CL, Patarroyo JC, Hirschberg DL, Brickey WJ, Soos JM, Piskurich JF, Chapman HA, Zamvil SS. The role of the MHC class II transactivator in class II expression and antigen presentation by astrocytes and in susceptibility to central nervous system autoimmune disease. J Immunol 2002;169(12):6720-6732.
64. Xiao BG, Diab A, Zhu J, van der MP, Link H. Astrocytes induce hyporesponses of myelin basic protein-reactive T-and B-cell function. J Neuroimmunol 1998;89(1-2):113-121.
65. Emerson MR, Gallagher RJ, Marquis JG, LeVine SM. Enhancing the ability of experimental autoimmune encephalomyelitis to serve as a more rigorous model of multiple sclerosis through refinement of the experimental design. Comp Med 2009;59(2):112-128.
66. Krishnamoorthy G, Wekerle H. EAE: An immunologist's magic eye. Eur J Immunol 2009;39(8):2031-2035.
67. Zhao ML, Fritz RB. Acute and relapsing experimental autoimmune encephalomyelitis in IL-4-and a/b T-cell-deficient C57BL/6 mice. J Neuroimmunol 1998;87(1-2): 171-178.
68. Jager A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK. Th1, Th17, and Th9-effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 2009;183(11):7169-7177.
69. Pollinger B, Krishnamoorthy G, Berer K, Lassmann H, Bosl MR, Dunn R, Domingues HS, Holz A, Kurschus FC, Wekerle H. Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells. J Exp Med 2009;206(6):1303-1316.
70. Bahbouhi B, Berthelot L, Pettre S, Michel L, Wiertlewski S, Weksler B, Romero IA, Miller F, Couraud PO, Brouard S, Laplaud DA, Soulillou JP. Peripheral blood CD4\+ T lymphocytes from multiple sclerosis patients are characterized by higher PSGL-1 expression and transmigration capacity across a human blood-brain barrier-derived endothelial cell line. J Leukoc Biol 2009;86(5):1049-1063.
71. Battistini L, Piccio L, Rossi B, Bach S, Galgani S, Gasperini C, Ottoboni L, Ciabini D, Caramia MD, Bernardi G, Laudanna C, Scarpini E, McEver RP, Butcher EC, Borsellino G, Constantin G. CD8\+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: A critical role for P-selectin glycoprotein ligand-1. Blood 2003;101(12):4775- 4782.
72. Steinman L. A molecular trio in relapse and remission in multiple sclerosis. Nat Rev Immunol 2009;9(6):440-447.
73. Vogt MH, Lopatinskaya L, Smits M, Polman CH, Nagelkerken L. Elevated osteopontin levels in active relap-sing-remitting multiple sclerosis. Ann Neurol 2003;53(6): 819-822.
74. Drulovic J, Savic E, Pekmezovic T, Mesaros S, Stojsavljevic N, Dujmovic-Basuroski I, Kostic J, Vasic V, Mostarica SM, Popadic D. Expression of Th1 and Th17 cytokines and transcription factors in multiple sclerosis patients: Does baseline T-bet mRNA predict the response to interferon-beta treatment? J Neuroimmunol 2009;215(1-2):90-95.
75. Whitaker JN. The presence of immunoreactive myelin basic protein peptide in urine of persons with multiple sclerosis. Ann Neurol 1987;22(5):648-655.