Advances in autoimmune myasthenia gravis management

References

• Sonkar KK, Bhoi SK, Dubey D, et al. Direct and indirect cost of myasthenia gravis: a prospective study from a tertiary care teaching hospital in India. J Clin Neurosci. 2017;38:114–117.
   PubMed Web of Science ®Google Scholar
• Alshekhlee A, Miles JD, Katirji B, et al. Incidence and mortality rates of myasthenia gravis and myasthenic crisis in US hospitals. Neurology. 2009;72:1548–1554.
   PubMed Web of Science ®Google Scholar
• Gilhus NE. Myasthenia gravis. N Engl J Med. 2016;375:2570–2581.
   Google Scholar
• Grob D, Brunner N, Namba T, et al. Lifetime course of myasthenia gravis. Muscle Nerve. 2008;37:141–149.
   PubMed Web of Science ®Google Scholar
• Mazzoli M, Ariatti A, Valzania F, et al. Factors affecting outcome in ocular myasthenia gravis. Int J Neurosci. 2018;128:15–24.
   PubMed Web of Science ®Google Scholar
• Sih M, Soliven B, Mathenia N, et al. Head-drop: a frequent feature of late-onset myasthenia gravis. Muscle Nerve. 2017;56:441–444.
   PubMed Web of Science ®Google Scholar
• Romano AE, Al-qudah z, kaminski hj, et al. concurrent paraspinous myopathy and myasthenia gravis. J Clin Neuromuscul Dis. 2017;18:218–222.
   PubMedGoogle Scholar
• Bershad EM, Feen ES, Suarez JI. Myasthenia gravis crisis. South Med J. 2008;101:63–69.
   PubMed Web of Science ®Google Scholar
• Evoli A, Tonali PA, Padua L, et al. Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. Brain. 2003;126:2304–2311.
   PubMed Web of Science ®Google Scholar
• Guptill JT, Sanders DB, Evoli A. Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts. Muscle Nerve. 2011;44:36–40.
   PubMed Web of Science ®Google Scholar
• Benatar M. A systematic review of diagnostic studies in myasthenia gravis. Neuromuscul Disord. 2006;16:459–467.
   PubMed Web of Science ®Google Scholar
• Phillips WD, Vincent A. Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms. F1000Res. 2016;5:1513.
   PubMedGoogle Scholar
• Zisimopoulou P, Evangelakou P, Tzartos J, et al. A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun. 2014;52:139–145.
   PubMed Web of Science ®Google Scholar
• Seybold ME. Diagnosis of myasthenia gravis. In: Engel AG, ed. Myasthenia gravis and myasthenic disorders. New York: Oxford University Press; 1999. p. 146–166.
   Google Scholar
• Meriggioli MN, Rowin J. Single fiber EMG as an outcome measure in myasthenia gravis: results from a double-blind, placebo-controlled trial. J Clin Neurophysiol. 2003;20:382–385.
   PubMed Web of Science ®Google Scholar
• Juel VC, Sanders DB, Hobson-Webb LD, et al. Marked clinical and jitter improvement after eculizumab in refractory myasthenia. Muscle Nerve. 2017;56:E16–E18.
   PubMed Web of Science ®Google Scholar
• Benatar M, Hammad M, Doss-Riney H. Concentric-needle single-fiber electromyography for the diagnosis of myasthenia gravis. Muscle Nerve. 2006;34:163–168.
   PubMed Web of Science ®Google Scholar
• Stalberg E, Sanders DB, Kouyoumdjian JA. Pitfalls and errors in measuring jitter. Clin Neurophysiol. 2017;128:2233–2241.
   PubMed Web of Science ®Google Scholar
• Patrick J, Lindstrom J. Autoimmune response to acetylcholine receptor. Science. 1973;180:871–872.
   PubMed Web of Science ®Google Scholar
• le Panse R, Berrih-Aknin S. Autoimmune myasthenia gravis: autoantibody mechanisms and new developments on immune regulation. Curr Opin Neurol. 2013;26:569–576.
   PubMed Web of Science ®Google Scholar
• Hoch W, McConville J, Helms S, et al. Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med. 2001;7:365–368.
   PubMed Web of Science ®Google Scholar
• Higuchi O, Hamuro J, Motomura M, et al. Autoantibodies to low-density lipoprotein receptor-related protein 4 in myasthenia gravis. Ann Neurol. 2011;69:418–422.
   PubMed Web of Science ®Google Scholar
• Pevzner A, Schoser B, Peters K, et al. Anti-LRP4 autoantibodies in AChR- and MuSK-antibody-negative myasthenia gravis. J Neurol. 2012;259:427–435.
   PubMed Web of Science ®Google Scholar
• Zhang B, Tzartos JS, Belimezi M, et al. Autoantibodies to lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch Neurol. 2012;69:445–451.
   PubMed Web of Science ®Google Scholar
• Rodriguez Cruz PM, Al-Hajjar M, Huda S, et al. Clinical features and diagnostic usefulness of antibodies to clustered acetylcholine receptors in the diagnosis of seronegative myasthenia gravis. JAMA Neurol. 2015;72:642–649.
   PubMed Web of Science ®Google Scholar
• Gilhus NE, Skeie GO, Romi F, et al. Myasthenia gravis - autoantibody characteristics and their implications for therapy. Nat Rev Neurol. 2016;12:259–268.
   PubMed Web of Science ®Google Scholar
• Cortes-Vicente E, Gallardo E, Martinez MA, et al. Clinical characteristics of patients with double-seronegative myasthenia gravis and antibodies to cortactin. JAMA Neurol. 2016;73:1099–1104.
   PubMed Web of Science ®Google Scholar
• Gallardo E, Martinez-Hernandez E, Titulaer MJ, et al. Cortactin autoantibodies in myasthenia gravis. Autoimmun Rev. 2014;13:1003–1007.
   PubMed Web of Science ®Google Scholar
• Verschuuren JJ, Palace J, Gilhus NE. Clinical aspects of myasthenia explained. Autoimmunity. 2010;43:344–352.
   PubMed Web of Science ®Google Scholar
• Lindstrom J. Acetylcholine receptors and myasthenia. Muscle Nerve. 2000;23:453–477.
   PubMed Web of Science ®Google Scholar
• Luo J, Lindstrom J. Myasthenogenicity of the main immunogenic region and endogenous muscle nicotinic acetylcholine receptors. Autoimmunity. 2011;45:245–252.
   PubMed Web of Science ®Google Scholar
• Kaminski HJ, Kusner LL, Nash KV, et al. The gamma-subunit of the acetylcholine receptor is not expressed in the levator palpebrae superioris. Neurology. 1995;45:516–518.
   PubMed Web of Science ®Google Scholar
• Bouzat C, Sine SM. Nicotinic acetylcholine receptors at the single-channel level. Br J Pharmacol. 2018;175:1789–1804.
   PubMed Web of Science ®Google Scholar
• Kordas G, Lagoumintzis G, Sideris S, et al. Direct proof of the in vivo pathogenic role of the AChR autoantibodies from myasthenia gravis patients. PLoS One. 2014;9:e108327.
   PubMed Web of Science ®Google Scholar
• Engel AG, Lambert EH, Howard FM. Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations. Mayo Clin Proc. 1977;52:267–280.
   PubMed Web of Science ®Google Scholar
• Kusner LL, Sengupta M, Kaminski HJ. Acetylcholine receptor antibody-mediated animal models of myasthenia gravis and the role of complement. Ann N Y Acad Sci. 2018;1413:136–142.
   PubMed Web of Science ®Google Scholar
• Howard JF Jr. Myasthenia gravis: the role of complement at the neuromuscular junction. Ann N Y Acad Sci. 2018;1412:113–128.
   PubMed Web of Science ®Google Scholar
• Loutrari H, Kokla A, Tzartos SJ. Passive transfer of experimental myasthenia gravis via antigenic modulation of acetylcholine receptor. Eur J Immunol. 1992;22:2449–2452.
   PubMed Web of Science ®Google Scholar
• Drachman DB, Angus CW, Adams RN, et al. Myasthenic antibodies cross-link acetylcholine receptors to accelerate degradation. N Engl J Med. 1978;298:1116–1122.
   PubMed Web of Science ®Google Scholar
• Gomez CM, Richman DP. Anti-acetylcholine receptor antibodies directed against the alpha-bungarotoxin binding site induce a unique form of experimental myasthenia. Proc Natl Acad Sci U S A. 1983;80:4089–4093.
   PubMed Web of Science ®Google Scholar
• Hara H, Hayashi K, Ohta K, et al. Detection and characterization of blocking-type anti-acetylcholine receptor antibodies in sera from patients with myasthenia gravis. Clin Chem. 1993;39:2053–2057.
   PubMed Web of Science ®Google Scholar
• Heldal AT, Eide GE, Romi F, et al. Repeated acetylcholine receptor antibody-concentrations and association to clinical myasthenia gravis development. PLoS One. 2014;9:e114060.
   PubMed Web of Science ®Google Scholar
• Sanders DB, Burns TM, Cutter GR, et al. Does change in AChR antibody level correlate with clinical change in MG? Muscle Nerve. 2013;49:30–34.
   PubMed Web of Science ®Google Scholar
• Punga AR, Lin S, Oliveri F, et al. Muscle-selective synaptic disassembly and reorganization in MuSK antibody positive MG mice. Exp Neurol. 2011;230:207–217.
   PubMed Web of Science ®Google Scholar
• Klooster R, Plomp JJ, Huijbers MG, et al. Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice. Brain. 2012;135:1081–1101.
   PubMed Web of Science ®Google Scholar
• Messeant J, Dobbertin A, Girard E, et al. MuSK frizzled-like domain is critical for mammalian neuromuscular junction formation and maintenance. J Neurosci. 2015;35:4926–4941.
   PubMed Web of Science ®Google Scholar
• Plomp JJ, Huijbers MG, Van Der Maarel SM, et al. Pathogenic IgG4 subclass autoantibodies in MuSK myasthenia gravis. Ann N Y Acad Sci. 2012;1275:114–122.
   PubMed Web of Science ®Google Scholar
• Huijbers MG, Vink AF, Niks EH, et al. Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity. J Neuroimmunol. 2016;291:82–88.
   PubMed Web of Science ®Google Scholar
• Deymeer F, Gungor-Tuncer O, Yilmaz V, et al. Clinical comparison of anti-MuSK- vs anti-AChR-positive and seronegative myasthenia gravis. Neurology. 2007;68:609–611.
   PubMed Web of Science ®Google Scholar
• Tzartos JS, Zisimopoulou P, Rentzos M, et al. LRP4 antibodies in serum and CSF from amyotrophic lateral sclerosis patients. Ann Clin Transl Neurol. 2014;1:80–87.
   PubMed Web of Science ®Google Scholar
• Shen C, Lu Y, Zhang B, et al. Antibodies against low-density lipoprotein receptor-related protein 4 induce myasthenia gravis. J Clin Invest. 2013;123:5190–5202.
   PubMed Web of Science ®Google Scholar
• Li Y, Zhang Y, Cai G, et al. Anti-LRP4 autoantibodies in Chinese patients with myasthenia gravis. Muscle Nerve. 2017;56:938–942.
   PubMed Web of Science ®Google Scholar
• Romi F, Hong Y, Gilhus NE. Pathophysiology and immunological profile of myasthenia gravis and its subgroups. Curr Opin Immunol. 2017;49:9–13.
   PubMed Web of Science ®Google Scholar
• Leite MI, Jacob S, Viegas S, et al. IgG1 antibodies to acetylcholine receptors in ‘seronegative’ myasthenia gravis. Brain. 2008;131:1940–1952.
   PubMed Web of Science ®Google Scholar
• Marx A, Pfister F, Schalke B, et al. The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev. 2013;12:875–884.
   PubMed Web of Science ®Google Scholar
• Truffault F, De Montpreville V, Eymard B, et al. Centers and corticosteroids in myasthenia gravis: an immunopathological study in 1035 cases and a critical review. Clin Rev Allergy Immunol. 2017;52:108–124.
   PubMed Web of Science ®Google Scholar
• Hogquist KA, Baldwin TA, Jameson SC. Central tolerance: learning self-control in the thymus. Nat Rev Immunol. 2005;5:772–782.
   PubMed Web of Science ®Google Scholar
• Klein L, Kyewski B, Allen PM, et al. Positive and negative selection of the T cell repertoire: what thymocytes see (and don’t see). Nat Rev Immunol. 2014;14:377–391.
   PubMed Web of Science ®Google Scholar
• Anderson MS, Venanzi ES, Klein L, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298:1395–1440.
   PubMed Web of Science ®Google Scholar
• Fujii Y. Thymus, thymoma and myasthenia gravis. Surg Today. 2013;43:461–466.
   PubMed Web of Science ®Google Scholar
• Strobel P, Murumagi A, Klein R, et al. Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). J Pathol. 2007;211:563–571.
   PubMed Web of Science ®Google Scholar
• Marx A, Porubsky S, Belharazem D, et al. Thymoma related myasthenia gravis in humans and potential animal models. Exp Neurol. 2015;270:55–65.
   PubMed Web of Science ®Google Scholar
• Marx A, Willcox N, Leite MI, et al. Thymoma and paraneoplastic myasthenia gravis. Autoimmunity. 2010;43:413–427.
   PubMed Web of Science ®Google Scholar
• Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015;14:1023–1036.
   PubMed Web of Science ®Google Scholar
• Cron MA, Maillard S, Villegas J, et al. Thymus involvement in early-onset myasthenia gravis. Ann N Y Acad Sci. 2018;1412:137–145.
   PubMed Web of Science ®Google Scholar
• Conti-Fine Bm, Milani M, Kaminski HJ. Myasthenia gravis: past, present, and future. J Clin Invest. 2006;116:2843–2854.
   PubMed Web of Science ®Google Scholar
• Lang B, Vincent A. Autoimmune disorders of the neuromuscular junction. Curr Opin Pharmacol. 2009;9:336–340.
   PubMed Web of Science ®Google Scholar
• Willcox N, Leite MI, Kadota Y, et al. Autoimmunizing mechanisms in thymoma and thymus. Ann N Y Acad Sci. 2008;1132:163–173.
   PubMed Web of Science ®Google Scholar
• Conti-Fine Bm, Diethelm-Okita B, Ostlie N, et al. Immunopathogenesis of myasthenia gravis. In: Hj K, ed. Myasthenia and related disorders. New York: Humana Press; 2009. p. 43–70.
   Google Scholar
• Poea-Guyon S, Christadoss P, le Panse R, et al. Effects of cytokines on acetylcholine receptor expression: implications for myasthenia gravis. J Immunol. 2005;174:5941–5949.
   PubMed Web of Science ®Google Scholar
• Le Panse R, Bismuth J, Cizeron-Clairac G, et al. Thymic remodeling associated with hyperplasia in myasthenia gravis. Autoimmunity. 2010;43:401–412.
   PubMed Web of Science ®Google Scholar
• Cufi P, Dragin N, Ruhlmann N, et al. Central role of interferon-beta in thymic events leading to myasthenia gravis. J Autoimmun. 2014;52:44–52.
   PubMed Web of Science ®Google Scholar
• Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016;375:2570–2581.
   PubMed Web of Science ®Google Scholar
• Yi JS, Guptill JT, Stathopoulos P, et al. B cells in the pathophysiology of myasthenia gravis. Muscle Nerve. 2018;57:172–184.
   PubMed Web of Science ®Google Scholar
• Leite MI, Strobel P, Jones M, et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol. 2005;57:444–448.
   PubMed Web of Science ®Google Scholar
• Han J, Sun L, Fan X, et al. Role of regulatory B cells in neuroimmunologic disorders. J Neurosci Res. 2016;94:693–701.
   PubMed Web of Science ®Google Scholar
• Sun F, Ladha SS, Yang L, et al. Interleukin-10 producing-B cells and their association with responsiveness to rituximab in myasthenia gravis. Muscle Nerve. 2014;49:487–494.
   PubMed Web of Science ®Google Scholar
• Fan X, Lin C, Han J, et al. Follicular helper CD4+ T cells in human neuroautoimmune diseases and their animal models. Mediators Inflamm. 2015;2015:638968.
   PubMedGoogle Scholar
• Cao Y, Amezquita RA, Kleinstein SH, et al. Autoreactive T cells from patients with myasthenia gravis are characterized by elevated IL-17, IFN-gamma, and GM-CSF and diminished IL-10 production. J Immunol. 2016;196:2075–2084.
   PubMed Web of Science ®Google Scholar
• 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 myasthenia gravis. Eur J Immunol. 2015;45:1339–1347.
   PubMed Web of Science ®Google Scholar
• Alahgholi-Hajibehzad M, Kasapoglu P, Jafari R, et al. The role of T regulatory cells in immunopathogenesis of myasthenia gravis: implications for therapeutics. Expert Rev Clin Immunol. 2015;11:859–870.
   PubMed Web of Science ®Google Scholar
• Alahgholi-Hajibehzad M, Oflazer P, Aysal F, et al. Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity. J Neuroimmunol. 2015;281:51–60.
   PubMed Web of Science ®Google Scholar
• Wen Y, Yang B, Lu J, et al. Imbalance of circulating CD4(+)CXCR5(+)FOXP3(+) Tfr-like cells and CD4(+)CXCR5(+)FOXP3(-) Tfh-like cells in myasthenia gravis. Neurosci Lett. 2016;630:176–182.
   PubMed Web of Science ®Google Scholar
• Portt L, Norman G, Clapp C, et al. Anti-apoptosis and cell survival: a review. Biochim Biophys Acta. 2011;1813:238–259.
   PubMed Web of Science ®Google Scholar
• Nagata T, Onodera H, Ohuchi M, et al. Decreased expression of c-myc family genes in thymuses from myasthenia gravis patients. J Neuroimmunol. 2001;115:199–202.
   PubMed Web of Science ®Google Scholar
• Salakou S, Tsamandas AC, Bonikos DS, et al. The potential role of bcl-2, bax, and Ki67 expression in thymus of patients with myasthenia gravis, and their correlation with clinicopathologic parameters. Eur J Cardiothorac Surg. 2001;20:712–721.
   PubMed Web of Science ®Google Scholar
• Kusner LL, Ciesielski MJ, Marx A, et al. Survivin as a potential mediator to support autoreactive cell survival in myasthenia gravis: a human and animal model study. PLoS One. 2014;9:e102231.
   PubMed Web of Science ®Google Scholar
• Pedersen J, LaCasse EC, Seidelin JB, et al. Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation. Trends Mol Med. 2014;20:652–665.
   PubMed Web of Science ®Google Scholar
• Gravina G, Wasen C, Garcia-Bonete MJ, et al. Survivin in autoimmune diseases. Autoimmun Rev. 2017;16:845–855.
   PubMed Web of Science ®Google Scholar
• Sussman J, Farrugia ME, Maddison P, et al. Myasthenia gravis: association of British Neurologists’ management guidelines. Pract Neurol. 2015;15:199–206.
   PubMedGoogle Scholar
• Murai H. Japanese clinical guidelines for myasthenia gravis: putting into practice. Clin Exp Neuroimmunol. 2015;2015:21–31.
   Google Scholar
• Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016;87:419–425.
   PubMed Web of Science ®Google Scholar
• Maggi L, Mantegazza R. Treatment of myasthenia gravis: focus on pyridostigmine. Clin Drug Investig. 2011;31:691–701.
   PubMed Web of Science ®Google Scholar
• Mehndiratta MM, Pandey S, Kuntzer T. Acetylcholinesterase inhibitor treatment for myasthenia gravis. Cochrane Database Syst Rev. 2014;13(10):CD006986.
   PubMed Web of Science ®Google Scholar
• Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized Trial of Thymectomy in Myasthenia Gravis. N Engl J Med. 2016;375:511–522.
   PubMed Web of Science ®Google Scholar
• Okumura M, Ohta M, Takeuchi Y, et al. The immunologic role of thymectomy in the treatment of myasthenia gravis: implication of thymus-associated B-lymphocyte subset in reduction of the anti-acetylcholine receptor antibody titer. J Thorac Cardiovasc Surg. 2003;126:1922–1928.
   PubMed Web of Science ®Google Scholar
• Evoli A, Bianchi MR, Riso R, et al. Response to therapy in myasthenia gravis with anti-MuSK antibodies. Ann N Y Acad Sci. 2008;1132:76–83.
   PubMed Web of Science ®Google Scholar
• Bedlack RS, Sanders DB. Steroids have an important role. Muscle Nerve. 2002;25:117–121.
   PubMed Web of Science ®Google Scholar
• Rivner MH. Steroids are overutilized. Muscle Nerve. 2002;25:115–117.
   PubMed Web of Science ®Google Scholar
• Schneider-Gold C, Gajdos P, Toyka KV, et al. Corticosteroids for myasthenia gravis. Cochrane Database Syst Rev. 2005;18(2):CD002828.
   PubMed Web of Science ®Google Scholar
• Hoffmann S, Kohler S, Ziegler A, et al. Glucocorticoids in myasthenia gravis - if, when, how, and how much? Acta Neurol Scand. 2014;130:211–221.
   PubMed Web of Science ®Google Scholar
• Evoli A, Batocchi AP, Palmisani MT, et al. Long-term results of corticosteroid therapy in patients with myasthenia gravis. Eur Neurol. 1992;32:37–43.
   PubMed Web of Science ®Google Scholar
• Xie Y, Li H-F, Sun L, et al. The role of osteopontin and its gene on glucorticoid response in myasthenia gravis. Front Neurol. 2017. DOI:10.3389/fneu.
   Web of Science ®Google Scholar
• Xie Y, Meng Y, Li HF, et al. GR gene polymorphism is associated with inter-subject variability in response to glucocorticoids in patients with myasthenia gravis. Eur J Neurol. 2016;23:1372–1379.
   PubMed Web of Science ®Google Scholar
• Imai T, Suzuki S, Tsuda E, et al. Oral corticosteroid therapy and present disease status in myasthenia gravis. Muscle Nerve. 2015;51:692–696.
   PubMed Web of Science ®Google Scholar
• Quax RA, Manenschijn L, Koper JW, et al. Glucocorticoid sensitivity in health and disease. Nat Rev Endocrinol. 2013;9:670–686.
   PubMed Web of Science ®Google Scholar
• Flammer JR, Rogatsky I. Minireview: glucocorticoids in autoimmunity: unexpected targets and mechanisms. Mol Endocrinol. 2011;25:1075–1086.
   PubMedGoogle Scholar
• Kaminski HJ, Alnosair E, Algahtani RM. Clinical trials for myasthenia gravis: a historical perspective. Ann N Y Acad Sci. 2018;1413:5–10.
   PubMed Web of Science ®Google Scholar
• Palace J, Newsom-Davis J, Lecky B. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. Neurology. 1998;50:1778–1783.
   Google Scholar
• Pelin M, de Iudicibus S, Londero M, et al. Thiopurine biotransformation and pharmacological effects: contribution of oxidative stress. Curr Drug Metab. 2016;17:542–549.
   PubMed Web of Science ®Google Scholar
• Shin JY, Wey M, Umutesi HG, et al. Thiopurine prodrugs mediate immunosuppressive effects by interfering with rac1 protein function. J Biol Chem. 2016;291:13699–13714.
   PubMed Web of Science ®Google Scholar
• Pedersen EG, Pottegard A, Hallas J, et al. Use of azathioprine for non-thymoma myasthenia and risk of cancer: a nationwide case-control study in Denmark. Eur J Neurol. 2013;20:942–948.
   PubMed Web of Science ®Google Scholar
• Machkhas H, Harati Y, Rolak LA. Clinical pharmacology of immunosuppressants: guidelines for neuroimmunotherapy. In: Rolak LA, Harati Y, eds. Neuroimmunology for the clinician. Boston: Butterworth Heinemann; 1997. p. 77–104.
   Google Scholar
• Jack KL, Koopman WJ, Hulley D, et al. A review of azathioprine-associated hepatotoxicity and myelosuppression in myasthenia gravis. J Clin Neuromuscul Dis. 2016;18:12–20.
   PubMedGoogle Scholar
• Norwood F, Dhanjal M, Hill M, et al. Myasthenia in pregnancy: best practice guidelines from a U.K. multispecialty working group. J Neurol Neurosurg Psychiatry. 2014;85:538–543.
   PubMed Web of Science ®Google Scholar
• Ciafaloni E, Massey JM, Tucker-Lipscomb B, et al. Mycophenolate mofetil for myasthenia gravis: an open-label pilot study. Neurology. 2001;56:97–99.
   PubMed Web of Science ®Google Scholar
• Chaudhry V, Cornblath DR, Griffin JW, et al. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases. Neurology. 2001;56:94–96.
   PubMed Web of Science ®Google Scholar
• Meriggioli MN, Rowin J, Richman JG, et al. Mycophenolate mofetil for myasthenia gravis: a double-blind, placebo-controlled pilot study. Ann N Y Acad Sci. 2003;998:494–499.
   PubMed Web of Science ®Google Scholar
• Chan JW. Mycophenolate mofetil for ocular myasthenia. J Neurol. 2008;255:510–513.
   PubMed Web of Science ®Google Scholar
• Sanders DB, Hart IK, Mantegazza R, et al. An international, phase III, randomized trial of mycophenolate mofetil in myasthenia gravis. Neurology. 2008;71:400–406.
   PubMed Web of Science ®Google Scholar
• Muscle Study Group. A trial of mycophenolate mofetil with prednisone as initial immunotherapy in myasthenia gravis. Neurology. 2008;71:394–399.
   PubMed Web of Science ®Google Scholar
• Benatar M, Rowland LP. The muddle of mycophenolate mofetil in myasthenia. Neurology. 2008;71:390–391.
   PubMed Web of Science ®Google Scholar
• Villarroel MC, Hidalgo M, Jimeno A. Mycophenolate mofetil: an update. Drugs Today (Barc). 2009;45:521–522.
   PubMed Web of Science ®Google Scholar
• Termsarasab P, Katirji B. Opportunistic infections in myasthenia gravis treated with mycophenolate mofetil. J Neuroimmunol. 2012;249:83–85.
   PubMed Web of Science ®Google Scholar
• Coscia La, Armenti Dp, King Rw, et al. Update on the Teratogenicity of Maternal Mycophenolate Mofetil. J Pediatr Genet. 2015;4:42–55.
   PubMed Web of Science ®Google Scholar
• Buell C, Koo J. Long-term safety of mycophenolate mofetil and cyclosporine: a review. J Drugs Dermatol. 2008;7:741–748.
   PubMed Web of Science ®Google Scholar
• O’Neill JO, Edwards LB, Taylor DO. Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the international society for heart and lung transplantation. J Heart Lung Transplant. 2006;25:1186–1191.
   PubMed Web of Science ®Google Scholar
• Vernino S, Salomao DR, Habermann TM, et al. Primary CNS lymphoma complicating treatment of myasthenia gravis with mycophenolate mofetil. Neurology. 2005;65:639–641.
   PubMed Web of Science ®Google Scholar
• Cruz JL, Wolff ML, Vanderman AJ, et al. The emerging role of tacrolimus in myasthenia gravis. Ther Adv Neurol Disord. 2015;8:92–103.
   PubMed Web of Science ®Google Scholar
• Yagi Y, Sanjo N, Yokota T, et al. Tacrolimus monotherapy: a promising option for ocular myasthenia gravis. Eur Neurol. 2013;69:344–345.
   PubMed Web of Science ®Google Scholar
• Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can’t live without. J Immunol. 2013;191:5785–5791.
   PubMed Web of Science ®Google Scholar
• Ponseti JM, Azem J, Fort JM, et al. Long-term results of tacrolimus in cyclosporine- and prednisone-dependent myasthenia gravis. Neurology. 2005;64:1641–1643.
   PubMed Web of Science ®Google Scholar
• Tindall RSA, Phillips JT, Rollins JA, et al. A clinical therapeutic trial of cyclosporine in myasthenia gravis. Ann NY Acad Sci. 1993;681:539–551.
   PubMed Web of Science ®Google Scholar
• Ciafaloni E, Nikhar NK, Massey JM, et al. Retrospective analysis of the use of cyclosporine in myasthenia gravis. Neurology. 2000;55:448–450.
   PubMed Web of Science ®Google Scholar
• Lavrnic D, Vujic A, Rakocevic-Stojanovic V, et al. Cyclosporine in the treatment of myasthenia gravis. Acta Neurol Scand. 2005;111:247–252.
   PubMed Web of Science ®Google Scholar
• Hart IK, Sathasivam S, Sharshar T. Immunosuppressive agents for myasthenia gravis. Cochrane Database Syst Rev. 2007;17(4):CD005224.
   PubMed Web of Science ®Google Scholar
• Tamler R, Epstein S. Nonsteroid immune modulators and bone disease. Ann N Y Acad Sci. 2006;1068:284–296.
   PubMed Web of Science ®Google Scholar
• Marder W, McCune WJ. Advances in immunosuppressive therapy. Semin Respir Crit Care Med. 2007;28:398–417.
   PubMed Web of Science ®Google Scholar
• Wessels JA, Huizinga TW, Guchelaar HJ. Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 2008;47:249–255.
   PubMed Web of Science ®Google Scholar
• Pasnoor M, He J, Herbelin L, et al. A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis. Neurology. 2016;87:57–64.
   PubMed Web of Science ®Google Scholar
• Heckmann JM, Rawoot A, Bateman K, et al. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC Neurol. 2011;11:97.
   PubMed Web of Science ®Google Scholar
• Nagappa M, Netravathi M, Taly AB, et al. Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis. J Clin Neurosci. 2014;21:1909–1914.
   PubMed Web of Science ®Google Scholar
• Drachman DB, Brodsky RA. High-dose therapy for autoimmune neurologic diseases. Curr Opin Oncol. 2005;17:83–88.
   PubMed Web of Science ®Google Scholar
• Bryant A, Atkins H, Pringle CE, et al. Myasthenia gravis treated with autologous hematopoietic stem cell transplantation. JAMA Neurol. 2016;73:652–658.
   PubMed Web of Science ®Google Scholar
• Sistigu A, Viaud S, Chaput N, et al. Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Semin Immunopathol. 2011;33:369–383.
   PubMed Web of Science ®Google Scholar
• Alabdali M, Barnett C, Katzberg H, et al. Intravenous immunoglobulin as treatment for myasthenia gravis: current evidence and outcomes. Expert Rev Clin Immunol. 2014;10:1659–1665.
   PubMed Web of Science ®Google Scholar
• Lunemann JD, Nimmerjahn F, Dalakas MC. Intravenous immunoglobulin in neurology–mode of action and clinical efficacy. Nat Rev Neurol. 2015;11:80–89.
   PubMed Web of Science ®Google Scholar
• Bril V, Barnett-Tapia C, Barth D, et al. IVIG and PLEX in the treatment of myasthenia gravis. Ann N Y Acad Sci. 2012;1275:1–6.
   PubMed Web of Science ®Google Scholar
• Barth D, Nabavi Nouri M, Ng E, et al. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. 2011;76:2017–2023.
   PubMed Web of Science ®Google Scholar
• Nadeau JO, Bhibhatbhan A, McDougall D, et al. Identification and comparison of adverse events for preparations of IVIG in patients with neuromuscular diseases. Clin Neurol Neurosurg. 2010;112:467–469.
   PubMed Web of Science ®Google Scholar
• Pinching AJ, Peters DK, Newsom-Davis J. Remission of myasthenia gravis following plasma exchange. Lancet. 1976;2:1373–1376.
   PubMed Web of Science ®Google Scholar
• Guptill JT, Oakley D, Kuchibhatla M, et al. A retrospective study of complications of therapeutic plasma exchange in myasthenia. Muscle Nerve. 2013;47:170–176.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Gong B, Lin F, et al. Anti-C5 antibody treatment ameliorates weakness in experimentally acquired myasthenia gravis. J Immunol. 2007;179:8562–8567.
   PubMed Web of Science ®Google Scholar
• Howard JF Jr., Utsugisawa K, Benatar M, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017;16:976–986.
   PubMed Web of Science ®Google Scholar
• Licht C, Greenbaum LA, Muus P, et al. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies. Kidney Int. 2015;87:1061–1073.
   PubMed Web of Science ®Google Scholar
• Ninomiya H, Obara N, Chiba S, et al. Interim analysis of post-marketing surveillance of eculizumab for paroxysmal nocturnal hemoglobinuria in Japan. Int J Hematol. 2016;104:548–558.
   PubMed Web of Science ®Google Scholar
• Nishimura J, Yamamoto M, Hayashi S, et al. Genetic variants in C5 and poor response to eculizumab. N Engl J Med. 2014;370:632–639.
   PubMed Web of Science ®Google Scholar
• Razzak M. Anaemia: mutations in C5 explain eculizumab resistance. Nat Rev Nephrol. 2014;10:182.
   PubMedGoogle Scholar
• Argov Z, McKee D, Agus S, et al. Treatment of human myasthenia gravis with oral antisense suppression of acetylcholinesterase. Neurology. 2007;69:699–700.
   PubMed Web of Science ®Google Scholar
• Boneva N, Hamra-Amitay Y, Wirguin I, et al. Stimulated-single fiber electromyography monitoring of anti-sense induced changes in experimental autoimmune myasthenia gravis. Neurosci Res. 2006;55:40–44.
   PubMed Web of Science ®Google Scholar
• Brenner T, Hamra-Amitay Y, Evron T, et al. The role of readthrough acetylcholinesterase in the pathophysiology of myasthenia gravis. FASEB J. 2003;17:214–222.
   PubMed Web of Science ®Google Scholar
• Somnier FE, Langvad E. Plasma exchange with selective immunoadsorption of anti-acetylcholine receptor antibodies. J Neuroimmunol. 1989;22:123–127.
   PubMed Web of Science ®Google Scholar
• Ptak J. Changes of plasma proteins after immunoadsorption using Ig-Adsopak columns in patients with myasthenia gravis. Transfus Apher Sci. 2004;30:125–129.
   PubMed Web of Science ®Google Scholar
• Antozzi C, Berta E, Confalonieri P, et al. Protein-A immunoadsorption in immunosuppression-resistant myasthenia gravis. Lancet. 1994;343:124.
   PubMed Web of Science ®Google Scholar
• Grob D, Simpson D, Mitsumoto H, et al. Treatment of myasthenia gravis by immunoadsorption of plasma. Neurology. 1995;45:338–344.
   PubMed Web of Science ®Google Scholar
• Lagoumintzis G, Zisimopoulou P, Kordas G, et al. Recent approaches to the development of antigen-specific immunotherapies for myasthenia gravis. Autoimmunity. 2010;43:436–445.
   PubMed Web of Science ®Google Scholar
• Lagoumintzis G, Zisimopoulou P, Trakas N, et al. Scale up and safety parameters of antigen specific immunoadsorption of human anti-acetylcholine receptor antibodies. J Neuroimmunol. 2014;267:1–6.
   PubMed Web of Science ®Google Scholar
• Lazaridis K, Evaggelakou P, Bentenidi E, et al. Specific adsorbents for myasthenia gravis autoantibodies using mutants of the muscle nicotinic acetylcholine receptor extracellular domains. J Neuroimmunol. 2015;278:19–25.
   PubMed Web of Science ®Google Scholar
• Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 2007;7:715–725.
   PubMed Web of Science ®Google Scholar
• Liu X, Ye L, Christianson GJ, et al. NF-kappaB signaling regulates functional expression of the MHC class I-related neonatal Fc receptor for IgG via intronic binding sequences. J Immunol. 2007;179:2999–3011.
   PubMed Web of Science ®Google Scholar
• Kusner LL, Satija N, Cheng G, et al. Targeting therapy to the neuromuscular junction: proof of concept. Muscle Nerve. 2014;49:749–756.
   PubMed Web of Science ®Google Scholar
• Song C, Xu Z, Miao J, et al. Protective effect of scFv-DAF fusion protein on the complement attack to acetylcholine receptor: a possible option for treatment of myasthenia gravis. Muscle Nerve. 2012;45:668–675.
   PubMed Web of Science ®Google Scholar
• Fredslund F, Laursen NS, Roversi P, et al. Structure of and influence of a tick complement inhibitor on human complement component 5. Nat Immunol. 2008;9:753–760.
   PubMed Web of Science ®Google Scholar
• Soltys J, Kusner LL, Young A, et al. Novel complement inhibitor limits severity of experimentally myasthenia gravis. Ann Neurol. 2009;65:67–75.
   PubMed Web of Science ®Google Scholar
• Subias M, Tortajada A, Gastoldi S, et al. A novel antibody against human factor B that blocks formation of the C3bB proconvertase and inhibits complement activation in disease models. J Immunol. 2014;193:5567–5575.
   PubMed Web of Science ®Google Scholar
• Huda R, Tuzun E, Christadoss P. Complement C2 siRNA mediated therapy of myasthenia gravis in mice. J Autoimmun. 2013;42:94–104.
   PubMed Web of Science ®Google Scholar
• Luo J, Lindstrom J. AChR-specific immunosuppressive therapy of myasthenia gravis. Biochem Pharmacol. 2015;97:609–619.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Ma CG, Zhang GX, Xiao BG, et al. Suppression of experimental autoimmune myasthenia gravis by nasal administration of acetylcholine receptor. J Neuroimmunol. 1995;58:51–60.
   PubMed Web of Science ®Google Scholar
• Okumura S, McIntosh K, Drachman DB. Oral administration of acetylcholine receptor: effects on experimental myasthenia gravis. Ann Neurol. 1994;36:704–713.
   PubMed Web of Science ®Google Scholar
• Wang ZY, Qiao J, Link H. Suppression of experimental autoimmune myasthenia gravis by oral administration of acetylcholine receptor. J Neuroimmunol. 1993;44:209–214.
   PubMed Web of Science ®Google Scholar
• Luo J, Kuryatov A, Lindstrom JM. Specific immunotherapy of experimental myasthenia gravis by a novel mechanism. Ann Neurol. 2010;67:441–451.
   PubMed Web of Science ®Google Scholar
• Luo J, Lindstrom J. Antigen-specific immunotherapeutic vaccine for experimental autoimmune myasthenia gravis. J Immunol. 2014;193:5044–5055.
   PubMed Web of Science ®Google Scholar
• Araga S, Blalock JE. Use of complementary peptides and their antibodies in B-cell-mediated autoimmune disease: prevention of experimental autoimmune myasthenia gravis with a peptide vaccine. Immunomethods. 1994;5:130–135.
   PubMedGoogle Scholar
• Araga S, leBoeuf RD, Blalock JE. Prevention of experimental autoimmune myasthenia gravis by manipulation of the immune network with a complementary peptide for the acetylcholine receptor. Proc Natl Acad Sci U S A. 1993;90:8747–8751.
   PubMed Web of Science ®Google Scholar
• Araga S, Xu L, Nakashima K, et al. A peptide vaccine that prevents experimental autoimmune myasthenia gravis by specifically blocking T cell help. FASEB J. 2000;14:185–196.
   PubMed Web of Science ®Google Scholar
• Galin FS, Chrisman CL, Cook JR Jr., et al. Possible therapeutic vaccines for canine myasthenia gravis: implications for the human disease and associated fatigue. Brain Behav Immun. 2007;21:323–331.
   PubMed Web of Science ®Google Scholar
• Shelton GD, Lindstrom JM. Spontaneous remission in canine myasthenia gravis: implications for assessing human MG therapies. Neurology. 2001;57:2139–2141.
   PubMed Web of Science ®Google Scholar
• Bongioanni P, Ricciardi R, Pellegrino D, et al. T-cell tumor necrosis factor-alpha receptor binding in myasthenic patients. J Neuroimmunol. 1999;93:203–207.
   PubMed Web of Science ®Google Scholar
• Li H, Shi FD, Bai X, et al. Cytokine and chemokine mRNA expressing cells in muscle tissues of experimental autoimmune myasthenia gravis. J Neurol Sci. 1998;161:40–46.
   PubMed Web of Science ®Google Scholar
• Christadoss P, Goluszko E. Treatment of experimental autoimmune myasthenia gravis with recombinant human tumor necrosis factor receptor Fc protein. J Neuroimmunol. 2002;122:186–190.
   PubMed Web of Science ®Google Scholar
• Rowin J, Meriggioli MN, Tuzun E, et al. Etanercept treatment in corticosteroid-dependent myasthenia gravis. Neurology. 2004;63:2390–2392.
   PubMed Web of Science ®Google Scholar
• Tuzun E, Meriggioli MN, Rowin J, et al. Myasthenia gravis patients with low plasma IL-6 and IFN-gamma benefit from etanercept treatment. J Autoimmun. 2005;24:261–268.
   PubMed Web of Science ®Google Scholar
• Fee DB, Kasarskis EJ. Myasthenia gravis associated with etanercept therapy. Muscle Nerve. 2009;39:866–870.
   PubMed Web of Science ®Google Scholar
• Kim JY, Yang Y, Moon JS, et al. Serum BAFF expression in patients with myasthenia gravis. J Neuroimmunol. 2008;199:151–154.
   PubMed Web of Science ®Google Scholar
• Ragheb S, Lisak R, Lewis R, et al. A potential role for B-cell activating factor in the pathogenesis of autoimmune myasthenia gravis. Arch Neurol. 2008;65:1358–1362.
   PubMedGoogle Scholar
• Ragheb S, Lisak RP. B-cell-activating factor and autoimmune myasthenia gravis. Autoimmune Dis. 2011;2011:939520.
   PubMedGoogle Scholar
• Berrih-Aknin S, Ragheb S, Le Panse R, et al. Ectopic germinal centers, BAFF and anti-B-cell therapy in myasthenia gravis. Autoimmun Rev. 2013;12:885–893.
   PubMed Web of Science ®Google Scholar
• Avidan N, Le Panse R, Harbo HF, et al. VAV1 and BAFF, via NFkappaB pathway, are genetic risk factors for myasthenia gravis. Ann Clin Transl Neurol. 2014;1:329–339.
   PubMed Web of Science ®Google Scholar
• Ibtehaj N, Huda R. High-dose BAFF receptor specific mAb-siRNA conjugate generates Fas-expressing B cells in lymph nodes and high-affinity serum autoantibody in a myasthenia mouse model. Clin Immunol. 2017;176:122–130.
   PubMed Web of Science ®Google Scholar
• Monson NL, Cravens PD, Frohman EM, et al. Effect of rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch Neurol. 2005;62:258–264.
   PubMed Web of Science ®Google Scholar
• Diaz-Manera J, Martinez-Hernandez E, Querol L, et al. Long-lasting treatment effect of rituximab in MuSK myasthenia. Neurology. 2012;78:189–193.
   PubMed Web of Science ®Google Scholar
• Hiepe F, Radbruch A. Plasma cells as an innovative target in autoimmune disease with renal manifestations. Nat Rev Nephrol. 2016;12:232–240.
   PubMed Web of Science ®Google Scholar
• Kane RC, Farrell AT, Sridhara R, et al. United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin Cancer Res. 2006;12:2955–2960.
   PubMed Web of Science ®Google Scholar
• Gomez AM, Willcox N, Vrolix K, et al. Proteasome inhibition with bortezomib depletes plasma cells and specific autoantibody production in primary thymic cell cultures from early-onset myasthenia gravis patients. J Immunol. 2014;193:1055–1063.
   PubMed Web of Science ®Google Scholar
• Gomez AM, Vrolix K, Martinez-Martinez P, et al. Proteasome inhibition with bortezomib depletes plasma cells and autoantibodies in experimental autoimmune myasthenia gravis. J Immunol. 2011;186:2503–2513.
   PubMed Web of Science ®Google Scholar
• Arastu-Kapur S, Anderl JL, Kraus M, et al. Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin Cancer Res. 2011;17:2734–2743.
   PubMed Web of Science ®Google Scholar
• Gomez AM, Willcox N, Molenaar PC, et al. Targeting plasma cells with proteasome inhibitors: possible roles in treating myasthenia gravis?. Ann N Y Acad Sci. 2012;1274:48–59.
   PubMed Web of Science ®Google Scholar
• Palumbo R, Gogliettino M, Cocca E, et al. APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome. Int J Mol Sci. 2016;17:E1614.
   PubMed Web of Science ®Google Scholar
• Krejcik J, Casneuf T, Nijhof IS, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128:384–394.
   PubMed Web of Science ®Google Scholar
• Thiruppathi M, Rowin J, Ganesh B, et al. Impaired regulatory function in circulating CD4(+)CD25(high)CD127(low/-) T cells in patients with myasthenia gravis. Clin Immunol. 2012;145:209–223.
   PubMed Web of Science ®Google Scholar
• Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–1132.
   PubMed Web of Science ®Google Scholar
• Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–1141.
   PubMed Web of Science ®Google Scholar
• Waite JC, Skokos D. Th17 response and inflammatory autoimmune diseases. Int J Inflam. 2012;2012:819467.
   PubMedGoogle Scholar
• Aguilo-Seara G, Xie Y, Sheehan J, et al. Ablation of IL-17 expression moderates experimental autoimmune myasthenia gravis disease severity. Cytokine. 2017;96:279–285.
   PubMed Web of Science ®Google Scholar
• Roche JC, Capablo JL, Larrad L, et al. Increased serum interleukin-17 levels in patients with myasthenia gravis. Muscle Nerve. 2011;44:278–280.
   PubMed Web of Science ®Google Scholar
• Gradolatto A, Nazzal D, Truffault F, et al. Both Treg cells and Tconv cells are defective in the Myasthenia gravis thymus: roles of IL-17 and TNF-alpha. J Autoimmun. 2014;52:53–63.
   PubMed Web of Science ®Google Scholar
• Xie Y, Li HF, Jiang B, et al. Elevated plasma interleukin-17A in a subgroup of Myasthenia Gravis patients. Cytokine. 2016;78:44–46.
   PubMed Web of Science ®Google Scholar
• Yi JS, Guidon A, Sparks S, et al. Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis. J Autoimmun. 2014;52:130–138.
   PubMed Web of Science ®Google Scholar
• Pinelli DF, Wakeman BS, Wagener ME, et al. Rapamycin ameliorates the CTLA4-Ig-mediated defect in CD8(+) T cell immunity during gammaherpesvirus infection. Am J Transplant. 2015;15:2576–2587.
   PubMed Web of Science ®Google Scholar
• Chen J, Yin H, Xu J, et al. Reversing endogenous alloreactive B cell GC responses with anti-CD154 or CTLA-4Ig. Am J Transplant. 2013;13:2280–2292.
   PubMed Web of Science ®Google Scholar
• Im SH, Barchan D, Maiti PK, et al. Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4. J Immunol. 2001;166:6893–6898.
   PubMed Web of Science ®Google Scholar
• Balandina A, Lecart S, Dartevelle P, et al. Functional defect of regulatory CD4(+)CD25+ T cells in the thymus of patients with autoimmune myasthenia gravis. Blood. 2005;105:735–741.
   PubMed Web of Science ®Google Scholar
• Sheng JR, Li L, Ganesh BB, et al. Suppression of experimental autoimmune myasthenia gravis by granulocyte-macrophage colony-stimulating factor is associated with an expansion of FoxP3+ regulatory T cells. J Immunol. 2006;177:5296–5306.
   PubMed Web of Science ®Google Scholar
• Sheng JR, Li LC, Ganesh BB, et al. Regulatory T cells induced by GM-CSF suppress ongoing experimental myasthenia gravis. Clin Immunol. 2008;128:172–180.
   PubMed Web of Science ®Google Scholar
• Sheng JR, Muthusamy T, Prabhakar BS, et al. GM-CSF-induced regulatory T cells selectively inhibit anti-acetylcholine receptor-specific immune responses in experimental myasthenia gravis. J Neuroimmunol. 2011;240-241:65–73.
   PubMed Web of Science ®Google Scholar
• Rowin J, Thiruppathi M, Arhebamen E, et al. Granulocyte macrophage colony-stimulating factor treatment of a patient in myasthenic crisis: effects on regulatory T cells. Muscle Nerve. 2012;46:449–453.
   PubMed Web of Science ®Google Scholar
• Strober J, Cowan MJ, Horn BN. Allogeneic hematopoietic cell transplantation for refractory myasthenia gravis. Arch Neurol. 2009;66:659–661.
   PubMedGoogle Scholar
• Hakansson I, Sandstedt A, Lundin F, et al. Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report. Neuromuscul Disord. 2017;27:90–93.
   PubMed Web of Science ®Google Scholar
• Benatar M, Sanders DB, Burns TM, et al. Recommendations for myasthenia gravis clinical trials. Muscle Nerve. 2012;45:909–917.
   PubMed Web of Science ®Google Scholar