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CHAPtER 65 Myasthenia Gravis 889

ON tHE HORIZON 11. Engel AG, Sahashi K, Fumagalli G. The immunopathology of acquired
myasthenia gravis. Ann NY Acad Sci 1981;377:158.
Development of Immunomodulatory Therapies 12. Drachman DB, Angus CW, Adams RN, et al. Myasthenic antibodies
cross-link acetylcholine receptors to accelerate degradation. N Engl J Med
• Complement inhibitors 1978;298:1116.
• Newly developed B-cell lineage inhibitors, including anti–plasma cell 13. Richman DP, Wollmann RL, Maselli RA, et al. Effector mechanisms of
monoclonal antibodies
• Acetylcholine receptor (AChR)–Fc fusion molecules myasthenic antibodies. Ann NY Acad Sci 1993;681:264.
• Inhibitors that target key immunopathogenic cytokines 14. Conti-Fine B, Navaneetham D, Karachunski PI, et al. T cell recognition
• AChR-specific immunosuppression of the acetylcholine receptor in myasthenia gravis. Ann NY Acad Sci
1998;841:283.
15. Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor.
Science 1973;180:871.
16. Christadoss P, Poussin M, Deng C. Animal models of myasthenia gravis.
development of novel therapies for use in the humans. MG Clin Immunol 2000;94:75.
occupies a unique position in the pantheon of autoimmune 17. Bellone M, Ostile N, Lei S, et al. Experimental myasthenia gravis in
diseases because of its strong association with thymic pathology. congenic mice. Sequence mapping and H-2 restriction of T helper
epitopes on the α subunits of Torpedo californica and murine
In MG-associated thymic hyperplasia, thymic events, particularly acetylcholine receptors. Eur J Immunol 1991;21:2303.
those leading to antecedent inflammation within the medulla, 18. Karachunski PI, Ostlie NS, Okita DK, et al. Interleukin-4 deficiency
likely serve as a driving force behind the development of the facilitates development of experimental myasthenia gravis and precludes
autoimmune process. Indeed, the overarching idea that tolerance its prevention by nasal administration of CD4+ epitope sequences of the
is breached in the thymus may be viewed as antithetical, given acetylcholine receptor. J Neuroimmunol 1999;95:73.
the established and critical role this organ plays in T-cell central 19. Wang W, Milani F, Ostlie G, et al. C57BL/6 mice genetically deficient in
tolerance. Unravelling the link between the thymus and MG will IL-12/IL-23 and IFN-γ are susceptible to experimental autoimmune
require further study. However, in the meantime, we can expect myasthenia gravis, suggesting a pathogenic role of non-Th1 cells.
that continued exploration of immune perturbations and their J Immunol 2007;178:7072.
underlying molecular mechanisms in animals with EAMG and 20. Schaffert H, Pelz A, Saxena A, et al. IL-17-producing CD4(+) T cells
contribute to the loss of B-cell tolerance in experimental autoimmune
in patients with MG will lead to safer and more robust therapeutic myasthenia gravis. Eur J Immunol 2015;45:1339.
interventions. 21. Levinson AI, Wheatley LM. The thymus and the pathogenesis of
myasthenia gravis. Clin Immunol Immunopathol 1995;78:1.
ACKNOWLEDGMENT 22. Berrih-Aknin S, Lepanse R. Myasthenia gravis: a comprehensive review
of immune dysregulation and etiological mechanisms. J Autoimmun
This work was supported by National Institutes of Health (NIH) 2014;52:90.
grant NS19546. 23. Marx A, Pfister F, Schalke B, et al. The different roles of the thymus in the
pathogenesis of the various myasthenia gravis subtypes. Autoimmunity
Please check your eBook at https://expertconsult.inkling.com/ Rev 2013;12:875.
for self-assessment questions. See inside cover for registration 24. Levinson AI, Zheng Y, Gaulton G, et al. Intrathymic expression of
neuromuscular acetylcholine receptors and the immunopathogenesis of
details. myasthenia gravis. Immunol Res 2003;27:399.
25. Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized trial of thymectomy
REFERENCES in myasthenia gravis. N Engl J Med 2016;375:511–22.
26. Levinson AI. Modeling the intrathymic pathogenesis of myasthenia
1. Lisak RP, Barchi RL. Myasthenia gravis. In: Walton JN, editor. Major gravis. J Neurolog Sci 2013;333:60.
problems in neurology, vol. 11. Philadelphia, PA: WB Saunders; 1982. 27. Chuang WY, Strobel P, Belharazem D, et al. The PTPN22gain-of-
p. 5. function+1858T(+) genotypes correlate with low IL-2 expression in
2. Engel A. The investigation of congenital myasthenic syndromes. Ann NY thymomas and predispose to myasthenia gravis. Genes Immun
Acad Sci 1993;681:425. 2009;10:667.
3. Levinson AI, Zweiman B, Lisak RP. Immunopathogenesis and treatment 28. Greve B, Hoffmann P, Illes Z, et al. The autoimmunity-related
of myasthenia gravis. J Clin Immunol 1987;7:187. polymorphism PTPN22 1858C/T is associated with anti-titin
4. Tindal RSA. Humoral immunity in myasthenia gravis: biochemical antibody-positive myasthenia gravis. Hum Immunol 2009;70:540.
characterization of acquired anti-receptor antibodies and clinical 29. Stefansson K, Dieperink ME, Richman DP, et al. Sharing of epitopes by
correlations. Ann Neurol 1981;10:437. bacteria and the nicotinic acetylcholine receptor: a possible role in the
5. Papadouli I, Sakarellos C, Tzartos SJ. High-resolution epitope mapping pathogenesis of myasthenia gravis. Ann NY Acad Sci 1987;505:451.
and fine antigenic characterization of the main immunogenic region of 30. Schwimmbeck PL, Dyrberg T, Drachman DB, et al. Molecular mimicry
the acetylcholine receptor. Eur J Biochem 1993;211:227. and myasthenia gravis: an autoantigenic site of the acetylcholine receptor
6. Leite MI, Jacob S, Viegas S, et al. IgG1 antibodies to acetylcholine α-subunit that has biologic activity and reacts immunochemically with
receptors in “seronegative” myasthenia gravis. Brain 2008;131:1940. herpes simplex virus. J Clin Invest 1989;84:1174.
7. Levinson AI, Lisak RP. Myasthenia gravis. In: Detrick B, Schmitz J, 31. Dwyer DS, Vakil M, Bradleg RT, et al. A possible cause of myasthenia
Hamilton RG, editors. Manual of molecular and clinical laboratory gravis: idiotypic networks involving bacterial antigens. Ann NY Acad Sci
immunology. 8th ed, ASM Press, 2016. 1987;505:461.
8. Sanders DB, Juel VC. MuSK-antibody positive myasthenia gravis: 32. Bever CT Jr, Chang HW, Penn AS, et al. Chemical alteration of
questions from the clinic. J Neuroimmunol 2008;201-202:85. acetylcholine receptor by penicillamine: a mechanism for induction of
9. Arrli JA, Skeie GO, Mygand A, et al. Muscle striation antibodies in myasthenia gravis. Neurology 1982;32:1077.
myasthenia gravis. Ann NY Acad Sci 1998;841:505. 33. Penn A, Jacques JJ. Cells from mice exposed chronically to
10. Drachman DB, Adams RN, Josifek LF, et al. Antibody-mediated D-penicillamine show proliferative responses to D-penicillamine-treated
mechanisms of ACh receptor loss in myasthenia gravis: clinical relevance. self (macrophage/dendritic cells): a graft-versus-host response? Ann NY
Ann NY Acad Sci 1981;377:175. Acad Sci 1993;681:319.