Experimental Autoimmune Myasthenia Gravis (EAMG): From immunochemical characterization to therapeutic approaches

Journal of Autoimmunity

Volumn 54, Issue , 2014, Pages 51-59

  Fuchs, Sara ^a   Aricha, Revital ^a   Reuveni, Debby ^a,b   Souroujon, Miriam C ^a,b  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b OPEN UNIVERSITY OF ISRAEL   (Israel)

Author keywords

Myasthenia gravis

Indexed keywords

ANTIGEN; ANTIIDIOTYPIC ANTIBODY; CD40 LIGAND MONOCLONAL ANTIBODY; CHEMOKINE RECEPTOR CXCR3 ANTAGONIST; CHOLINERGIC RECEPTOR; IMMUNOGLOBULIN G; INTERLEUKIN 6 ANTIBODY; INTERLEUKIN 8 ANTIBODY; METHYLPREDNISOLONE SODIUM SUCCINATE; MONOCLONAL ANTIBODY; NICOTINIC RECEPTOR ALPHA; PHOSPHODIESTERASE INHIBITOR; UNCLASSIFIED DRUG; AUTOANTIBODY; NICOTINIC RECEPTOR;

ANTIBODY RESPONSE; CELLULAR IMMUNITY; DRUG EFFECT; ELECTRIC FISH; EXPERIMENTAL AUTOIMMUNE MYASTHENIA GRAVIS; HUMAN; HUMORAL IMMUNITY; IMMUNOCHEMISTRY; IMMUNOMODULATION; IMMUNOTHERAPY; NONHUMAN; REGULATORY T LYMPHOCYTE; REVIEW; ANIMAL; DRUG EFFECTS; IMMUNOLOGY; MYASTHENIA GRAVIS, AUTOIMMUNE, EXPERIMENTAL; PATHOLOGY;

ANIMALS; ANTIBODIES, ANTI-IDIOTYPIC; ANTIBODIES, MONOCLONAL; AUTOANTIBODIES; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, HUMORAL; MYASTHENIA GRAVIS, AUTOIMMUNE, EXPERIMENTAL; RECEPTORS, NICOTINIC;

EID: 84908466794     PISSN: 08968411     EISSN: 10959157     Source Type: Journal    
DOI: 10.1016/j.jaut.2014.06.003     Document Type: Review

References (83)

1. Sela M., Arnon R. Aspecific synthetic polypeptide antigen. Biochim Biophys Acta 1960, 40:382-384.
2. Sela M. Antigenicity: some molecular aspects. Science 1969, 166:1365-1374.
3. Sela M., Fuchs S., Arnon R. Studies on the chemical basis of the antigenicity of proteins. 5. Synthesis, characterization and immunogenicity of some multichain and linear polypeptides containing tyrosine. Biochem J 1962, 85:223-235.
4. Klett R.P., Fulpius B.W., Cooper D., Smith M., Reich E., Possani L.D. The acetylcholine receptor. I. Purification and characterization of a macromolecule isolated from Electrophorus electricus. JBiol Chem 1973, 248:6841-6853.
5. Maoz A., Fuchs S., Sela M. On immunological cross-reactions between the synthetic ordered polypeptide (L-Pro-Gly-L-Pro)n and several collagens. Biochemistry 1973, 12:4246-4252.
6. Patrick J., Lindstrom J. Autoimmune response to acetylcholine receptor. Science 1973, 180:871-872.
7. Fuchs S. Immunology of the nicotinic acetylcholine receptor. Curr Top Microbiol Immunol 1979, 85:1-29.
8. Aharonov A., Tarrab-Hazdai R., Silman I., Fuchs S. Immunochemical studies on acetylcholine receptor from torpedo californica. Immunochemistry 1977, 14:129-137.
9. Lennon V.A., Lindstrom J.M., Seybold M.E. Experimental autoimmune myasthenia: a model of myasthenia gravis in rats and guinea pigs. JExp Med 1975, 141:1365-1375.
10. Tarrab-Hazdi R., Aharonov A., Abramsky O., Yaar I., Fuchs S. Passive transfer of experimental autoimmune myasthenia by lymph node cells in inbred guinea pigs. JExp Med 1975, 142:785-789.
11. Tarrab-Hazdai R., Aharonov A., Silman I., Fuchs S., Abramsky O. Experimental autoimmune myasthenia induced in monkeys by purified acetylcholine receptor. Nature 1975, 256:128-130.
12. Fuchs S., Nevo D., Tarrab-Hazdai R., Yaar I. Strain differences in the autoimmune response of mice to acetylcholine receptors. Nature 1976, 263:329-330.
13. Burres S.A., Crayton J.W., Gomez C.M., Richman D.P. Myasthenia induced by monoclonal anti-acetylcholine receptor antibodies: clinical and electrophysiological aspects. Ann Neurol 1981, 9:563-568.
14. Souroujon M.C., Pachner A.R., Fuchs S. The treatment of passively transferred experimental myasthenia with anti-idiotypic antibodies. Neurology 1986, 36:622-625.
15. Aricha R., Feferman T., Scott H.S., Souroujon M.C., Berrih-Aknin S., Fuchs S. The susceptibility of Aire(-/-) mice to experimental myasthenia gravis involves alterations in regulatory T cells. JAutoimmun 2011, 36:16-24.
16. Wu B., Goluszko E., Huda R., Tuzun E., Christadoss P. Experimental autoimmune myasthenia gravis in the mouse. Curr Protoc Immunol 2011, Chapter 15: Unit 15 23 Suppl. 100, 15.8.1-15.8.26.
17. Abramsky O., Aharonov A., Webb C., Fuchs S. Cellular immune response to acetylcholine receptor-rich fraction, in patients with myasthenia gravis. Clin Exp Immunol 1975, 19:11-16.
18. Aharonov A., Abramsky O., Tarrab-Hazdai R., Fuchs S. Humoral antibodies to acetylcholine receptor in patients with myasthenia gravis. Lancet 1975, 2:340-342.
19. Brenner T., Abramsky O., Lisak R.P., Zweiman B., Tarrab-Hazdai R., Fuchs S. Radioimmunoassay of antibodies to acetylcholine receptor in serum of myasthenia gravis patients. Isr J Med Sci 1978, 14:986-989.
20. Fuchs S., Bartfeld D., Mochly-Rosen D., Souroujon M., Feingold C. Acetylcholine receptor: molecular dissection and monoclonal antibodies in the study of experimental myasthenia. Ann N Y Acad Sci 1981, 377:110-124.
21. Moshly-Rosen D., Fuchs S., Eshhar Z. Monoclonal antibodies against defined determinants of acetylcholine receptor. FEBS Lett 1979, 106:389-392.
22. Tzartos S.J., Lindstrom J.M. Monoclonal antibodies used to probe acetylcholine receptor structure: localization of the main immunogenic region and detection of similarities between subunits. Proc Natl Acad Sci U S A 1980, 77:755-759.
23. Mochly-Rosen D., Fuchs S. Monoclonal anti-acetylcholine-receptor antibodies directed against the cholinergic binding site. Biochemistry 1981, 20:5920-5924.
24. Barkas T., Gabriel J.M., Mauron A., Hughes G.J., Roth B., Alliod C., et al. Monoclonal antibodies to the main immunogenic region of the nicotinic acetylcholine receptor bind to residues 61-76 of the alpha subunit. JBiol Chem 1988, 263:5916-5920.
25. Abramsky O., Aharonov A., Teitelbaum D., Fuchs S. Myasthenia gravis and acetylcholine receptor. Effect of steroids in clinical course and cellular immune response to acetylcholine receptor. Arch Neurol 1975, 32:684-687.
26. Abramsky O., Tarrab-Hazdai R., Aharonov A., Fuchs S. Immunosuppression of experimental autoimmune myasthenia gravis by hydrocortisone and azathioprine. JImmunol 1976, 117:225-228.
27. Bartfeld D., Fuchs S. Specific immunosuppression of experimental autoimmune myasthenia gravis by denatured acetylcholine receptor. Proc Natl Acad Sci U S A 1978, 75:4006-4010.
28. Schwartz M., Novick D., Givol D., Fuchs S. Induction of anti-idiotypic antibodies by immunisation with syngeneic spleen cells educated with acetylcholine receptor. Nature 1978, 273:543-545.
29. Mantegazza R., Bonanno S., Camera G., Antozzi C. Current and emerging therapies for the treatment of myasthenia gravis. Neuropsychiatr Dis Treat 2011, 7:151-160.
30. Weiner H.L. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 1997, 18:335-343.
31. Im S.H., Barchan D., Fuchs S., Souroujon M.C. Suppression of ongoing experimental myasthenia by oral treatment with an acetylcholine receptor recombinant fragment. JClin Invest 1999, 104:1723-1730.
32. Im S.H., Barchan D., Fuchs S., Souroujon M.C. Mechanism of nasal tolerance induced by a recombinant fragment of acetylcholine receptor for treatment of experimental myasthenia gravis. JNeuroimmunol 2000, 111:161-168.
33. Drachman D.B., Okumura S., Adams R.N., McIntosh K.R. Oral tolerance in myasthenia gravis. Ann N Y Acad Sci 1996, 778:258-272.
34. Barchan D., Asher O., Tzartos S.J., Fuchs S., Souroujon M.C. Modulation of the anti-acetylcholine receptor response and experimental autoimmune myasthenia gravis by recombinant fragments of the acetylcholine receptor. Eur J Immunol 1998, 28:616-624.
35. Barchan D., Souroujon M.C., Im S.H., Antozzi C., Fuchs S. Antigen-specific modulation of experimental myasthenia gravis: nasal tolerization with recombinant fragments of the human acetylcholine receptor alpha-subunit. Proc Natl Acad Sci U S A 1999, 96:8086-8091.
36. Abbas A.K., Murphy K.M., Sher A. Functional diversity of helper T lymphocytes. Nature 1996, 383:787-793.
37. O'Garra A. Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 1998, 8:275-283.
38. Maiti P.K., Feferman T., Im S.H., Souroujon M.C., Fuchs S. Immunosuppression of rat myasthenia gravis by oral administration of a syngeneic acetylcholine receptor fragment. JNeuroimmunol 2004, 152:112-120.
39. Im S.H., Barchan D., Feferman T., Raveh L., Souroujon M.C., Fuchs S. Protective molecular mimicry in experimental myasthenia gravis. JNeuroimmunol 2002, 126:99-106.
40. Souroujon M.C., Brenner T., Fuchs S. Development of novel therapies for MG: studies in animal models. Autoimmunity 2010, 43:446-460.
41. Feferman T., Im S.H., Fuchs S., Souroujon M.C. Breakage of tolerance to hidden cytoplasmic epitopes of the acetylcholine receptor in experimental autoimmune myasthenia gravis. JNeuroimmunol 2003, 140:153-158.
42. Vanderlugt C.L., Miller S.D. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2002, 2:85-95.
43. Souroujon M.C., Barchan D., Fuchs S. Analysis and modulation of the immune response of mice to acetylcholine receptor by anti-idiotypes. Immunol Lett 1985, 9:331-336.
44. Souroujon M.C., Fuchs S. Idiotypes and anti-idiotypes in experimental autoimmune myasthenia gravis. Ann N Y Acad Sci 1986, 475:81-93.
45. Souroujon M.C., Fuchs S. Antiidiotypic antibodies in the regulation of experimental autoimmune myasthenia gravis. Ann N Y Acad Sci 1987, 505:676-682.
46. Dalakas M.C. The use of intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: evidence-based indications and safety profile. Pharmacol Ther 2004, 102:177-193.
47. Kazatchkine M.D., Kaveri S.V. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. NEngl J Med 2001, 345:747-755.
48. Lemieux R., Bazin R., Neron S. Therapeutic intravenous immunoglobulins. Mol Immunol 2005, 42:839-848.
49. Fuchs S., Feferman T., Zhu K.Y., Meidler R., Margalit R., Wang N., et al. Suppression of experimental autoimmune myasthenia gravis by intravenous immunoglobulin and isolation of a disease-specific IgG fraction. Ann N Y Acad Sci 2007, 1110:550-558.
50. Zhu K.Y., Feferman T., Maiti P.K., Souroujon M.C., Fuchs S. Intravenous immunoglobulin suppresses experimental myasthenia gravis: immunological mechanisms. JNeuroimmunol 2006, 176:187-197.
51. Fuchs S., Feferman T., Meidler R., Brenner T., Laub O., Souroujon M.C. The disease-specific arm of the therapeutic effect of intravenous immunoglobulin in autoimmune diseases: experimental autoimmune myasthenia gravis as a model. Isr Med Assoc J 2008, 10:58-60.
52. Fuchs S., Feferman T., Meidler R., Margalit R., Sicsic C., Wang N., et al. Adisease-specific fraction isolated from IVIG is essential for the immunosuppressive effect of IVIG in experimental autoimmune myasthenia gravis. JNeuroimmunol 2008, 194:89-96.
53. Im S.H., Barchan D., Maiti P.K., Raveh L., Souroujon M.C., Fuchs S. Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune disease, by blockade of IL-18. FASEB J 2001, 15:2140-2148.
54. Im S.H., Barchan D., Maiti P.K., Fuchs S., Souroujon M.C. Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4. JImmunol 2001, 166:6893-6898.
55. Feferman T., Maiti P.K., Berrih-Aknin S., Bismuth J., Bidault J., Fuchs S., et al. Interferon-induced protein 10 (IP-10) and its receptor, CXCR3 are overexpressed in myasthenia gravis: new targets for immunotherapy. JImmunol 2005, 174:5324-5331.
56. Lennon V.A., Lambert E.H., Leiby K.R., Okarma T.B., Talib S. Recombinant human acetylcholine receptor alpha-subunit induces chronic experimental autoimmune myasthenia gravis. JImmunol 1991, 146:2245-2248.
57. Grewal I.S., Flavell R.A. The role of CD40 ligand in costimulation and T-cell activation. Immunol Rev 1996, 153:85-106.
58. Shi F.D., He B., Li H., Matusevicius D., Link H., Ljunggren H.G. Differential requirements for CD28 and CD40 ligand in the induction of experimental autoimmune myasthenia gravis. Eur J Immunol 1998, 28:3587-3593.
59. Shi F.D., Takeda K., Akira S., Sarvetnick N., Ljunggren H.G. IL-18 directs autoreactive T cells and promotes autodestruction in the central nervous system via induction of IFN-gamma by NK cells. JImmunol 2000, 165:3099-3104.
60. Luster A.D. Chemokines-chemotactic cytokines that mediate inflammation. NEngl J Med 1998, 338:436-445.
61. Neville L.F., Mathiak G., Bagasra O. The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth Factor Rev 1997, 8:207-219.
62. Feferman T., Aricha R., Mizrachi K., Geron E., Alon R., Souroujon M.C., et al. Suppression of experimental autoimmune myasthenia gravis by inhibiting the signaling between IFN-gamma inducible protein 10 (IP-10) and its receptor CXCR3. JNeuroimmunol 2009, 209:87-95.
63. Aricha R., Mizrachi K., Fuchs S., Souroujon M.C. Blocking of IL-6 suppresses experimental autoimmune myasthenia gravis. JAutoimmun 2011, 36:135-141.
64. Aricha R., Feferman T., Souroujon M.C., Fuchs S. Overexpression of phosphodiesterases in experimental autoimmune myasthenia gravis: suppression of disease by a phosphodiesterase inhibitor. FASEB J 2006, 20:374-376.
65. Ekholm D., Hemmer B., Gao G., Vergelli M., Martin R., Manganiello V. Differential expression of cyclic nucleotide phosphodiesterase 3 and 4 activities in human T cell clones specific for myelin basic protein. JImmunol 1997, 159:1520-1529.
66. Doherty A.M. Phosphodiesterase 4 inhibitors as novel anti-inflammatory agents. Curr Opin Chem Biol 1999, 3:466-473.
67. Mizrachi K., Aricha R., Feferman T., Kela-Madar N., Mandel I., Paperna T., et al. Involvement of phosphodiesterases in autoimmune diseases. JNeuroimmunol 2010, 220:43-51.
68. Menon R.T., Feferman T., Aricha R., Souroujon M.C., Fuchs S. Suppression of experimental autoimmune myasthenia gravis by combination therapy: pentoxifylline as a steroid-sparing agent. JNeuroimmunol 2008, 201-202:128-135.
69. Fattorossi A., Battaglia A., Buzzonetti A., Ciaraffa F., Scambia G., Evoli A. Circulating and thymic CD4 CD25 T regulatory cells in myasthenia gravis: effect of immunosuppressive treatment. Immunology 2005, 116:134-141.
70. Luther C., Poeschel S., Varga M., Melms A., Tolosa E. Decreased frequency of intrathymic regulatory T cells in patients with myasthenia-associated thymoma. JNeuroimmunol 2005, 164:124-128.
71. Sun Y., Qiao J., Lu C.Z., Zhao C.B., Zhu X.M., Xiao B.G. Increase of circulating CD4+CD25+ T cells in myasthenia gravis patients with stability and thymectomy. Clin Immunol 2004, 112:284-289.
72. Balandina A., Lecart S., Dartevelle P., Saoudi A., Berrih-Aknin S. Functional defect of regulatory CD4+CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood 2005, 105:735-741.
73. Ben-David H., Aruna B.V., Seger R., Sela M., Mozes E. A50-kDa ERK-like protein is up-regulated by a dual altered peptide ligand that suppresses myasthenia gravis-associated responses. Proc Natl Acad Sci U S A 2006, 103:18232-18237.
74. Liu R., La Cava A., Bai X.F., Jee Y., Price M., Campagnolo D.I., et al. Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia. JImmunol 2005, 175:7898-7904.
75. Sheng J.R., Li L., Ganesh B.B., Vasu C., Prabhakar B.S., Meriggioli M.N. Suppression of experimental autoimmune myasthenia gravis by granulocyte-macrophage colony-stimulating factor is associated with an expansion of FoxP3+ regulatory T cells. JImmunol 2006, 177:5296-5306.
76. Shi F.D., Li H., Wang H., Bai X., van der Meide P.H., Link H., et al. Mechanisms of nasal tolerance induction in experimental autoimmune myasthenia gravis: identification of regulatory cells. JImmunol 1999, 162:5757-5763.
77. Wang W., Milani M., Ostlie N., Okita D., Agarwal R.K., Caspi R., et al. C57BL/6 mice genetically deficient in IL-12/IL-23 and IFN-gamma are susceptible to experimental autoimmune myasthenia gravis, suggesting a pathogenic role of non-Th1 cells. JImmunol 2007, 178:7072-7080.
78. Zhang G.X., Xiao B.G., Yu L.Y., van der Meide P.H., Link H. Interleukin 10 aggravates experimental autoimmune myasthenia gravis through inducing Th2 and B cell responses to AChR. JNeuroimmunol 2001, 113:10-18.
79. Gertel-Lapter S., Mizrachi K., Berrih-Aknin S., Fuchs S., Souroujon M.C. Impairment of regulatory T cells in myasthenia gravis: studies in an experimental model. Autoimmun Rev 2013, 12:894-903.
80. Aricha R., Feferman T., Fuchs S., Souroujon M.C. Exvivo generated regulatory T cells modulate experimental autoimmune myasthenia gravis. JImmunol 2008, 180:2132-2139.
81. Jamin C., Renaudineau Y., Pers J.O. Pierre Youinou: when intuition and determination meet autoimmunity. JAutoimmun 2012, 39:117-120.
82. Invernizzi P. Liver auto-immunology: the paradox of autoimmunity in a tolerogenic organ. JAutoimmun 2013, 46:1-6.
83. Gershwin M.E., Shoenfeld Y. Abul Abbas: an epitome of scholarship. JAutoimmun 2013, 45:1-6.