Advertisement

General Principles of Immunotherapy in Neurological Diseases

Chapter
Part of the Contemporary Clinical Neuroscience book series (CCNE)

Abstract

Immunotherapy has changed the prognosis and outcome of many neuroimmunological diseases. In neurology, Immunotherapy aims to suppress or modulate the immune system. Due to the heterogeneity of immunological diseases, not all of the therapeutics are equally suited for different disorders. Thus, it is of importance to understand the pathophysiological and immunological background of the underlying disease as well as the mode of action of the various therapeutic agents. The aim of this chapter is to give an overview on the fundamental principles of the immune system. Selected diseases are presented to show the variety of the respective pathophysiological concepts. The last part describes the immunotherapies that are frequently used in neuroimmunological diseases with the mode of action and effects on the immune system. This chapter is addressed to clinicians who treat neuroimmunological disorders and shall facilitate the decision to find the right drug for the right patient.

Keywords

Neuroimmunology Immunotherapy Innate immune system Adaptive immune system Hematopoietic stem cell transplantation Anti-CD20 antibodies Alemtuzumab Glucocorticosteroids Mycophenolate mofetil Azathioprine Cyclophosphamide Tocilizumab Cladribine Dimethyl fumarate Teriflunomide IVIg Plasma exchange Interferon beta Glatiramer acetate Tocilizumab Natalizumab 

References

  1. 1.
    Definition of Immunotherapy [Internet]. MedicineNet. [cited 2018 Oct 8]. Available from: https://www.medicinenet.com/script/main/art.asp?articlekey=7824
  2. 2.
    Gold R, Buttgereit F, Toyka KV. Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders. J Neuroimmunol. 2001;117(1–2):1–8.PubMedGoogle Scholar
  3. 3.
    Drug Approval Package: Betaseron Interferon BETA-1B Subcutaneous (Generic Name) NDA # 103471 [Internet]. [cited 2018 Nov 12]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/103471s0000TOC.cfm
  4. 4.
    Rommer PS, Patejdl R, Zettl UK. Monoclonal antibodies in the treatment of neuroimmunological diseases. Curr Pharm Des. 2012;18(29):4498–507.PubMedGoogle Scholar
  5. 5.
    Rommer PS, Zettl UK. Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients. Expert Opin Pharmacother. 2018;19(5):483–98.PubMedGoogle Scholar
  6. 6.
    Parkin J, Cohen B. An overview of the immune system. Lancet. 2001;357(9270):1777–89.PubMedGoogle Scholar
  7. 7.
    Marshall JS, Warrington R, Watson W, Kim HL. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):49.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Carow CE, Hangoc G, Broxmeyer HE. Human multipotential progenitor cells (CFU-GEMM) have extensive replating capacity for secondary CFU-GEMM: an effect enhanced by cord blood plasma. Blood. 1993;81(4):942–9.PubMedGoogle Scholar
  9. 9.
    Kawamoto H, Minato N. Myeloid cells. Int J Biochem Cell Biol. 2004;36(8):1374–9.PubMedGoogle Scholar
  10. 10.
    Chaplin DD. Overview of the immune response. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S3–23.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Mattner J. Natural killer T (NKT) cells in autoimmune hepatitis. Curr Opin Immunol. 2013;25(6):697–703.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Perl A. Pathogenesis and spectrum of autoimmunity. Methods Mol Biol. 2012;900:1–9.PubMedGoogle Scholar
  13. 13.
    Warrington R, Watson W, Kim HL, Antonetti FR. An introduction to immunology and immunopathology. Allergy Asthma Clin Immunol. 2011;7(Suppl 1):S1.PubMedPubMedCentralGoogle Scholar
  14. 14.
    LeBien TW, Tedder TF. B lymphocytes: how they develop and function. Blood. 2008;112(5):1570–80.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Di Cesare A, Di Meglio P, Nestle FO. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129(6):1339–50.PubMedGoogle Scholar
  16. 16.
    Golubovskaya V, Wu L. Different subsets of T cells, memory, effector functions, and CAR-T immunotherapy. Cancer. 2016;8(3)PubMedCentralGoogle Scholar
  17. 17.
    Shibata K. Close link between development and function of gamma-delta T cells. Microbiol Immunol. 2012;56(4):217–27.PubMedGoogle Scholar
  18. 18.
    Shibata K, Yamada H, Nakamura M, Hatano S, Katsuragi Y, Kominami R, et al. IFN-γ-producing and IL-17-producing γδ T cells differentiate at distinct developmental stages in murine fetal thymus. J Immunol. 2014;192(5):2210–8.PubMedGoogle Scholar
  19. 19.
    Wiede F, Dudakov JA, Lu K-H, Dodd GT, Butt T, Godfrey DI, et al. PTPN2 regulates T cell lineage commitment and αβ versus γδ specification. J Exp Med. 2017;214(9):2733–58.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Cellular and molecular immunology – 9th edition [Internet]. [cited 2018 Dec 4]. Available from: https://www.elsevier.com/books/cellular-and-molecular-immunology/abbas/978-0-323-47978-3
  21. 21.
    Reinhardt RL, Liang H-E, Locksley RM. Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol. 2009;10(4):385–93.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Yang S-H, Gao C-Y, Li L, Chang C, Leung PSC, Gershwin ME, et al. The molecular basis of immune regulation in autoimmunity. Clin Sci. 2018;132(1):43–67.PubMedGoogle Scholar
  23. 23.
    Khan U, Ghazanfar H. T lymphocytes and autoimmunity. Int Rev Cell Mol Biol. 2018;341:125–68.PubMedGoogle Scholar
  24. 24.
    von Boehmer H, Melchers F. Checkpoints in lymphocyte development and autoimmune disease. Nat Immunol. 2010;11(1):14–20.Google Scholar
  25. 25.
    Passos GA, Speck-Hernandez CA, Assis AF, Mendes-da-Cruz DA. Update on Aire and thymic negative selection. Immunology. 2018;153(1):10–20.PubMedGoogle Scholar
  26. 26.
    Murphy KM, Travers P, Walport M. Janeway’s immunobiology (immunobiology: the immune system (Janeway)).Google Scholar
  27. 27.
    Xiang Z, Yang Y, Chang C, Lu Q. The epigenetic mechanism for discordance of autoimmunity in monozygotic twins. J Autoimmun. 2017;83:43–50.PubMedGoogle Scholar
  28. 28.
    Kinnunen E, Juntunen J, Ketonen L, Koskimies S, Konttinen YT, Salmi T, et al. Genetic susceptibility to multiple sclerosis. A co-twin study of a nationwide series. Arch Neurol. 1988;45(10):1108–11.PubMedGoogle Scholar
  29. 29.
    Williams A, Eldridge R, McFarland H, Houff S, Krebs H, McFarlin D. Multiple sclerosis in twins. Neurology. 1980;30(11):1139–47.PubMedGoogle Scholar
  30. 30.
    Multiple sclerosis in 54 twinships: concordance rate is independent of zygosity. French Research Group on Multiple Sclerosis. Ann Neurol. 1992;32(6):724–7.Google Scholar
  31. 31.
    Westerlind H, Ramanujam R, Uvehag D, Kuja-Halkola R, Boman M, Bottai M, et al. Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden. Brain J Neurol. 2014;137(Pt 3):770–8.Google Scholar
  32. 32.
    O’Gorman C, Lin R, Stankovich J, Broadley SA. Modelling genetic susceptibility to multiple sclerosis with family data. Neuroepidemiology. 2013;40(1):1–12.PubMedGoogle Scholar
  33. 33.
    Yu P. The potential role of retroviruses in autoimmunity. Immunol Rev. 2016;269(1):85–99.PubMedGoogle Scholar
  34. 34.
    Correale J, Gaitán MI. Multiple sclerosis and environmental factors: the role of vitamin D, parasites, and Epstein-Barr virus infection. Acta Neurol Scand. 2015;132(199):46–55.PubMedGoogle Scholar
  35. 35.
    Pane JA, Coulson BS. Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes. Diabetologia. 2015;58(6):1149–59.PubMedGoogle Scholar
  36. 36.
    Floreani A, Leung PSC, Gershwin ME. Environmental basis of autoimmunity. Clin Rev Allergy Immunol. 2016;50(3):287–300.PubMedGoogle Scholar
  37. 37.
    Wekerle H. Brain autoimmunity and intestinal microbiota: 100 trillion game changers. Trends Immunol. 2017;38(7):483–97.PubMedGoogle Scholar
  38. 38.
    Ramanathan S, Dale RC, Brilot F. Anti-MOG antibody: the history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmun Rev. 2016;15(4):307–24.PubMedGoogle Scholar
  39. 39.
    Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T. Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in multiple sclerosis group. N Engl J Med. 1998;339(5):285–91.Google Scholar
  40. 40.
    Fischer-Betz R, Specker C. Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome. Best Pract Res Clin Rheumatol. 2017;31(3):397–414.PubMedGoogle Scholar
  41. 41.
    Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018;378(2):169–80.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Bar-Or A. The immunology of multiple sclerosis. Semin Neurol. 2008;28(1):29–45.PubMedGoogle Scholar
  43. 43.
    Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M, Preston-Hurlburt P, et al. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J Clin Invest. 2013;123(6):2737–41.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Frohman EM, Racke MK, Raine CS. Multiple sclerosis – the plaque and its pathogenesis. N Engl J Med. 2006;354(9):942–55.Google Scholar
  45. 45.
    Luster AD, Alon R, von Andrian UH. Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol. 2005;6(12):1182–90.PubMedGoogle Scholar
  46. 46.
    Ransohoff RM, Engelhardt B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol. 2012;12(9):623–35.Google Scholar
  47. 47.
    Kabat EA, Moore DH, Landow H. An electrophoretic study of the protein components in cerebrospinal fluid and their relationship to the serum proteins. J Clin Invest. 1942;21(5):571–7.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Cepok S, Rosche B, Grummel V, Vogel F, Zhou D, Sayn J, et al. Short-lived plasma blasts are the main B cell effector subset during the course of multiple sclerosis. Brain J Neurol. 2005;128(Pt 7):1667–76.Google Scholar
  49. 49.
    Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung H-P, Hemmer B, et al. Ocrelizumab versus interferon Beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221–34.Google Scholar
  50. 50.
    Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209–20.Google Scholar
  51. 51.
    Reindl M, Khalil M, Berger T. Antibodies as biological markers for pathophysiological processes in MS. J Neuroimmunol. 2006;180(1–2):50–62.PubMedGoogle Scholar
  52. 52.
    Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain J Neurol. 2007;130(Pt 5):1235–43.Google Scholar
  53. 53.
    Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106–12.Google Scholar
  54. 54.
    Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain J Neurol. 2008;131(Pt 11):3072–80.Google Scholar
  55. 55.
    Saini H, Rifkin R, Gorelik M, Huang H, Ferguson Z, Jones MV, et al. Passively transferred human NMO-IgG exacerbates demyelination in mouse experimental autoimmune encephalomyelitis. BMC Neurol. 2013;13:104.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Stellmann J-P, Krumbholz M, Friede T, Gahlen A, Borisow N, Fischer K, et al. Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response. J Neurol Neurosurg Psychiatry. 2017;88(8):639–47.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Leypoldt F, Wandinger K-P, Bien CG, Dalmau J. Autoimmune encephalitis. Eur Neurol Rev. 2013;8(1):31–7.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Graus F, Saiz A. Limbic encephalitis: a probably under-recognized syndrome. Neurologia. 2005;20(1):24–30.PubMedGoogle Scholar
  59. 59.
    Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391–404.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Gebauer C, Pignolet B, Yshii L, Mauré E, Bauer J, Liblau R. CD4+ and CD8+ T cells are both needed to induce paraneoplastic neurological disease in a mouse model. Oncoimmunology. 2017;6(2):e1260212.CrossRefGoogle Scholar
  61. 61.
    Nguyen TP, Taylor RS. Guillain Barre syndrome. In: StatPearls [Internet]. Treasure Island: StatPearls Publishing; 2018 [cited 2018 Oct 26]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK532254/
  62. 62.
    Sinha S, Prasad KN, Jain D, Pandey CM, Jha S, Pradhan S. Preceding infections and anti-ganglioside antibodies in patients with Guillain-Barré syndrome: a single Centre prospective case-control study. Clin Microbiol Infect. 2007;13(3):334–7.PubMedGoogle Scholar
  63. 63.
    Goodfellow JA, Willison HJ. Guillain-Barré syndrome: a century of progress. Nat Rev Neurol. 2016;12(12):723–31.PubMedGoogle Scholar
  64. 64.
    Gilhus NE. Myasthenia gravis. N Engl J Med. 2016;375(26):2570–81.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Cetin H, Vincent A. Pathogenic mechanisms and clinical correlations in autoimmune myasthenic syndromes. Semin Neurol. 2018;38(3):344–54.Google Scholar
  66. 66.
    Rommer PS, Stüve O, Goertsches R, Mix E, Zettl UK. Monoclonal antibodies in the therapy of multiple sclerosis: an overview. J Neurol. 2008;255(Suppl 6):28–35.PubMedGoogle Scholar
  67. 67.
    Sorensen PS, Lisby S, Grove R, Derosier F, Shackelford S, Havrdova E, et al. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a phase 2 study. Neurology. 2014;82(7):573–81.Google Scholar
  68. 68.
    Home – ClinicalTrials.gov [Internet]. [cited 2018 Nov 2]. Available from: https://clinicaltrials.gov/
  69. 69.
    Genovese MC, Kaine JL, Lowenstein MB, Del Giudice J, Baldassare A, Schechtman J, et al. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I/II randomized, blinded, placebo-controlled, dose-ranging study. Arthritis Rheum. 2008;58(9):2652–61.PubMedGoogle Scholar
  70. 70.
    Greenberg BM, Graves D, Remington G, Hardeman P, Mann M, Karandikar N, et al. Rituximab dosing and monitoring strategies in neuromyelitis optica patients: creating strategies for therapeutic success. Mult Scler. 2012;18(7):1022–6.PubMedGoogle Scholar
  71. 71.
    Lehmann-Horn K, Kinzel S, Weber MS. Deciphering the role of B cells in multiple sclerosis-towards specific targeting of pathogenic function. Int J Mol Sci. 2017;18(10)PubMedPubMedCentralGoogle Scholar
  72. 72.
    Buggins AGS, Mufti GJ, Salisbury J, Codd J, Westwood N, Arno M, et al. Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab. Blood. 2002;100(5):1715–20.PubMedGoogle Scholar
  73. 73.
    Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Dyer MJ, et al. Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H. Leuk Res. 1998;22(2):185–91.PubMedGoogle Scholar
  74. 74.
    Rao SP, Sancho J, Campos-Rivera J, Boutin PM, Severy PB, Weeden T, et al. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis. PLoS One. 2012;7(6):e39416.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Ruck T, Bittner S, Wiendl H, Meuth SG. Alemtuzumab in multiple sclerosis: mechanism of action and beyond. Int J Mol Sci. 2015;16(7):16414–39.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Zhang X, Tao Y, Chopra M, Ahn M, Marcus KL, Choudhary N, et al. Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis. J Immunol. 2013;191(12):5867–74.PubMedGoogle Scholar
  77. 77.
    Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, et al. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006;253(1):98–108.PubMedGoogle Scholar
  78. 78.
    Thompson SAJ, Jones JL, Cox AL, Compston DAS, Coles AJ. B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. J Clin Immunol. 2010;30(1):99–105.PubMedGoogle Scholar
  79. 79.
    von Kutzleben S, Pryce G, Giovannoni G, Baker D. Depletion of CD52-positive cells inhibits the development of central nervous system autoimmune disease, but deletes an immune-tolerance promoting CD8 T-cell population. Implications for secondary autoimmunity of alemtuzumab in multiple sclerosis. Immunology. 2017;150(4):444–55.Google Scholar
  80. 80.
    Ziemssen T, Thomas K. Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world. Ther Adv Neurol Disord. 2017;10(10):343–59.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, Bar-Or A, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016;388(10044):576–85.PubMedGoogle Scholar
  82. 82.
    Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Steinmiller KC, et al. High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS. Neurology. 2017;88(9):842–52.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Burt RK, Loh Y, Pearce W, Beohar N, Barr WG, Craig R, et al. Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases. JAMA. 2008;299(8):925–36.PubMedGoogle Scholar
  84. 84.
    Armitage JO. Bone marrow transplantation. N Engl J Med. 1994;330(12):827–38.PubMedGoogle Scholar
  85. 85.
    Blanco Y, Saiz A, Carreras E, Graus F. Autologous haematopoietic-stem-cell transplantation for multiple sclerosis. Lancet Neurol. 2005;4(1):54–63.PubMedGoogle Scholar
  86. 86.
    Yong VW, Chabot S, Stuve O, Williams G. Interferon beta in the treatment of multiple sclerosis: mechanisms of action. Neurology. 1998;51(3):682–9.PubMedGoogle Scholar
  87. 87.
    Massey JC, Sutton IJ, Ma DDF, Moore JJ. Regenerating immunotolerance in multiple sclerosis with autologous hematopoietic stem cell transplant. Front Immunol. 2018;9:410.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Collins F, Kazmi M, Muraro PA. Progress and prospects for the use and the understanding of the mode of action of autologous hematopoietic stem cell transplantation in the treatment of multiple sclerosis. Expert Rev Clin Immunol. 2017;13(6):611–22.PubMedGoogle Scholar
  89. 89.
    Invernizzi P, Benedetti MD, Poli S, Monaco S. Azathioprine in multiple sclerosis. Mini Rev Med Chem. 2008;8(9):919–26.PubMedGoogle Scholar
  90. 90.
    Rajabally YA. Unconventional treatments for chronic inflammatory demyelinating polyneuropathy. Neurodegener Dis Manag. 2017;7(5):331–42.PubMedGoogle Scholar
  91. 91.
    Friedman AB, Sparrow MP, Gibson PR. The role of thiopurine metabolites in inflammatory bowel disease and rheumatological disorders. Int J Rheum Dis. 2014;17(2):132–41.PubMedGoogle Scholar
  92. 92.
    Wagner M, Earley AK, Webster AC, Schmid CH, Balk EM, Uhlig K. Mycophenolic acid versus azathioprine as primary immunosuppression for kidney transplant recipients. Cochrane Database Syst Rev. 2015;(12):CD007746.Google Scholar
  93. 93.
    Pelin M, De Iudicibus S, Londero M, Spizzo R, Dei Rossi S, Martelossi S, et al. Thiopurine biotransformation and pharmacological effects: contribution of oxidative stress. Curr Drug Metab. 2016;17(6):542–9.PubMedGoogle Scholar
  94. 94.
    Elion GB. The purine path to chemotherapy. Science. 1989;244(4900):41–7.PubMedGoogle Scholar
  95. 95.
    Schwartz R, Stack J, Dameshek W. Effect of 6-mercaptopurine on antibody production. Proc Soc Exp Biol Med. 1958;99(1):164–7.PubMedGoogle Scholar
  96. 96.
    Lord JD, Shows DM. Thiopurine use associated with reduced B and natural killer cells in inflammatory bowel disease. World J Gastroenterol. 2017;23(18):3240–51.PubMedPubMedCentralGoogle Scholar
  97. 97.
    Duley JA, Florin THJ. Thiopurine therapies: problems, complexities, and progress with monitoring thioguanine nucleotides. Ther Drug Monit. 2005;27(5):647–54.PubMedGoogle Scholar
  98. 98.
    Ertz-Archambault N, Kosiorek H, Taylor GE, Kelemen K, Dueck A, Castro J, et al. Association of therapy for autoimmune disease with myelodysplastic syndromes and acute myeloid leukemia. JAMA Oncol. 2017;3(7):936–43.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Kwong Y-L. Azathioprine: association with therapy-related myelodysplastic syndrome and acute myeloid leukemia. J Rheumatol. 2010;37(3):485–90.PubMedGoogle Scholar
  100. 100.
    Katara P, Kuntal H. TPMT polymorphism: when shield becomes weakness. Interdiscip Sci Comput Life Sci. 2016;8(2):150–5.Google Scholar
  101. 101.
    Yang S-K, Hong M, Baek J, Choi H, Zhao W, Jung Y, et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014;46(9):1017–20.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Leist TP, Weissert R. Cladribine: mode of action and implications for treatment of multiple sclerosis. Clin Neuropharmacol. 2011;34(1):28–35.PubMedGoogle Scholar
  103. 103.
    Kawasaki H, Carrera CJ, Piro LD, Saven A, Kipps TJ, Carson DA. Relationship of deoxycytidine kinase and cytoplasmic 5′-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. Blood. 1993;81(3):597–601.PubMedGoogle Scholar
  104. 104.
    Carson DA, Wasson DB, Taetle R, Yu A. Specific toxicity of 2-chlorodeoxyadenosine toward resting and proliferating human lymphocytes. Blood. 1983;62(4):737–43.PubMedGoogle Scholar
  105. 105.
    Lotfi K, Juliusson G, Albertioni F. Pharmacological basis for cladribine resistance. Leuk Lymphoma. 2003;44(10):1705–12.PubMedGoogle Scholar
  106. 106.
    Wiendl H. Cladribine – an old newcomer for pulsed immune reconstitution in MS. Nat Rev Neurol. 2017;13(10):573–4.PubMedGoogle Scholar
  107. 107.
    Ceronie B, Jacobs BM, Baker D, Dubuisson N, Mao Z, Ammoscato F, et al. Cladribine treatment of multiple sclerosis is associated with depletion of memory B cells. J Neurol. 2018;265(5):1199–209.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Laugel B, Borlat F, Galibert L, Vicari A, Weissert R, Chvatchko Y, et al. Cladribine inhibits cytokine secretion by T cells independently of deoxycytidine kinase activity. J Neuroimmunol. 2011;240–241:52–7.PubMedGoogle Scholar
  109. 109.
    Liliemark J. The clinical pharmacokinetics of cladribine. Clin Pharmacokinet. 1997;32(2):120–31.PubMedGoogle Scholar
  110. 110.
    Sistigu A, Viaud S, Chaput N, Bracci L, Proietti E, Zitvogel L. Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Semin Immunopathol. 2011;33(4):369–83.PubMedGoogle Scholar
  111. 111.
    Awad A, Stüve O. Cyclophosphamide in multiple sclerosis: scientific rationale, history and novel treatment paradigms. Ther Adv Neurol Disord. 2009;2(6):50–61.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Stankiewicz JM, Kolb H, Karni A, Weiner HL. Role of immunosuppressive therapy for the treatment of multiple sclerosis. Neurotherapeutics. 2013;10(1):77–88.PubMedGoogle Scholar
  113. 113.
    Ficken MD, Barnes HJ. Effect of cyclophosphamide on selected hematologic parameters of the Turkey. Avian Dis. 1988;32(4):812–7.PubMedGoogle Scholar
  114. 114.
    Unger C, Eibl H, von Heyden HW, Krisch B, Nagel GA. Blood-brain barrier and the penetration of cytostatic drugs. Klin Wochenschr. 1985;63(12):565–71.PubMedGoogle Scholar
  115. 115.
    Zephir H, de Seze J, Duhamel A, Debouverie M, Hautecoeur P, Lebrun C, et al. Treatment of progressive forms of multiple sclerosis by cyclophosphamide: a cohort study of 490 patients. J Neurol Sci. 2004;218(1–2):73–7.PubMedGoogle Scholar
  116. 116.
    Kanter IC, Huttner HB, Staykov D, Biermann T, Struffert T, Kerling F, et al. Cyclophosphamide for anti-GAD antibody-positive refractory status epilepticus. Epilepsia. 2008;49(5):914–20.PubMedGoogle Scholar
  117. 117.
    Lehmann JCU, Listopad JJ, Rentzsch CU, Igney FH, von Bonin A, Hennekes HH, et al. Dimethylfumarate induces immunosuppression via glutathione depletion and subsequent induction of heme oxygenase 1. J Invest Dermatol. 2007;127(4):835–45.PubMedGoogle Scholar
  118. 118.
    Schmidt TJ, Ak M, Mrowietz U. Reactivity of dimethyl fumarate and methylhydrogen fumarate towards glutathione and N-acetyl-L-cysteine – preparation of S-substituted thiosuccinic acid esters. Bioorg Med Chem. 2007;15(1):333–42.PubMedGoogle Scholar
  119. 119.
    Dubey D, Kieseier BC, Hartung HP, Hemmer B, Warnke C, Menge T, et al. Dimethyl fumarate in relapsing-remitting multiple sclerosis: rationale, mechanisms of action, pharmacokinetics, efficacy and safety. Expert Rev Neurother. 2015;15(4):339–46.PubMedGoogle Scholar
  120. 120.
    Mills EA, Ogrodnik MA, Plave A, Mao-Draayer Y. Emerging understanding of the mechanism of action for dimethyl fumarate in the treatment of multiple sclerosis. Front Neurol. 2018;9:5.PubMedPubMedCentralGoogle Scholar
  121. 121.
    Smith MD, Calabresi PA, Bhargava P. Dimethyl fumarate treatment alters NK cell function in multiple sclerosis. Eur J Immunol. 2018;48(2):380–3.PubMedGoogle Scholar
  122. 122.
    Wu Q, Wang Q, Mao G, Dowling CA, Lundy SK, Mao-Draayer Y. Dimethyl fumarate selectively reduces memory T cells and shifts the balance between Th1/Th17 and Th2 in multiple sclerosis patients. J Immunol. 2017;198(8):3069–80.PubMedPubMedCentralGoogle Scholar
  123. 123.
    Diebold M, Sievers C, Bantug G, Sanderson N, Kappos L, Kuhle J, et al. Dimethyl fumarate influences innate and adaptive immunity in multiple sclerosis. J Autoimmun. 2018;86:39–50.PubMedGoogle Scholar
  124. 124.
    Holm Hansen R, Højsgaard Chow H, Sellebjerg F, Rode von Essen M. Dimethyl fumarate therapy suppresses B cell responses and follicular helper T cells in relapsing-remitting multiple sclerosis. Mult Scler 2018;1352458518790417.Google Scholar
  125. 125.
    Smith MD, Martin KA, Calabresi PA, Bhargava P. Dimethyl fumarate alters B-cell memory and cytokine production in MS patients. Ann Clin Transl Neurol. 2017;4(5):351–5.PubMedPubMedCentralGoogle Scholar
  126. 126.
    Galloway DA, Williams JB, Moore CS. Effects of fumarates on inflammatory human astrocyte responses and oligodendrocyte differentiation. Ann Clin Transl Neurol. 2017;4(6):381–91.PubMedPubMedCentralGoogle Scholar
  127. 127.
    Brennan MS, Matos MF, Richter KE, Li B, Scannevin RH. The NRF2 transcriptional target, OSGIN1, contributes to monomethyl fumarate-mediated cytoprotection in human astrocytes. Sci Rep. 2017;7:42054.PubMedPubMedCentralGoogle Scholar
  128. 128.
    Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25(11):1256–64.PubMedGoogle Scholar
  129. 129.
    Jordan A, Freimer M. Recent advances in understanding and managing myasthenia gravis. F1000Res. 2018;7.Google Scholar
  130. 130.
    Howard JF, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, 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(12):976–86.PubMedGoogle Scholar
  131. 131.
    Soliris | European Medicines Agency [Internet]. [cited 2018 Dec 6]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/soliris#overview-section
  132. 132.
    Soliris (eculizumab) FDA Approval History [Internet]. Drugs.com. [cited 2018 Dec 6]. Available from: https://www.drugs.com/history/soliris.html
  133. 133.
    Pilch KS, Spaeth PJ, Yuki N, Wakerley BR. Therapeutic complement inhibition: a promising approach for treatment of neuroimmunological diseases. Expert Rev Neurother. 2017;17(6):579–91.PubMedGoogle Scholar
  134. 134.
    Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427(6972):355–60.PubMedGoogle Scholar
  135. 135.
    Schwab SR, Cyster JG. Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol. 2007;8(12):1295–301.PubMedGoogle Scholar
  136. 136.
    Kappos L, Antel J, Comi G, Montalban X, O’Connor P, Polman CH, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006;355(11):1124–40.PubMedGoogle Scholar
  137. 137.
    Cohen JA, Barkhof F, Comi G, Hartung H-P, Khatri BO, Montalban X, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.Google Scholar
  138. 138.
    Luessi F, Kraus S, Trinschek B, Lerch S, Ploen R, Paterka M, et al. FTY720 (fingolimod) treatment tips the balance towards less immunogenic antigen-presenting cells in patients with multiple sclerosis. Mult Scler. 2015;21(14):1811–22.PubMedGoogle Scholar
  139. 139.
    Claes N, Dhaeze T, Fraussen J, Broux B, Van Wijmeersch B, Stinissen P, et al. Compositional changes of B and T cell subtypes during fingolimod treatment in multiple sclerosis patients: a 12-month follow-up study. PLoS One. 2014;9(10):e111115.PubMedPubMedCentralGoogle Scholar
  140. 140.
    Serpero LD, Filaci G, Parodi A, Battaglia F, Kalli F, Brogi D, et al. Fingolimod modulates peripheral effector and regulatory T cells in MS patients. J Neuroimmune Pharmacol. 2013;8(5):1106–13.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Sato DK, Nakashima I, Bar-Or A, Misu T, Suzuki C, Nishiyama S, et al. Changes in Th17 and regulatory T cells after fingolimod initiation to treat multiple sclerosis. J Neuroimmunol. 2014;268(1–2):95–8.PubMedGoogle Scholar
  142. 142.
    Yamagata K, Tagami M, Torii Y, Takenaga F, Tsumagari S, Itoh S, et al. Sphingosine 1-phosphate induces the production of glial cell line-derived neurotrophic factor and cellular proliferation in astrocytes. Glia. 2003;41(2):199–206.PubMedGoogle Scholar
  143. 143.
    Edsall LC, Pirianov GG, Spiegel S. Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation. J Neurosci. 1997;17(18):6952–60.PubMedPubMedCentralGoogle Scholar
  144. 144.
    Colombo E, Di Dario M, Capitolo E, Chaabane L, Newcombe J, Martino G, et al. Fingolimod may support neuroprotection via blockade of astrocyte nitric oxide. Ann Neurol. 2014;76(3):325–37.PubMedGoogle Scholar
  145. 145.
    Teitelbaum D, Meshorer A, Hirshfeld T, Arnon R, Sela M. Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur J Immunol. 1971;1(4):242–8.PubMedGoogle Scholar
  146. 146.
    Aharoni R, Teitelbaum D, Arnon R, Sela M. Copolymer 1 acts against the immunodominant epitope 82-100 of myelin basic protein by T cell receptor antagonism in addition to major histocompatibility complex blocking. Proc Natl Acad Sci U S A. 1999;96(2):634–9.PubMedPubMedCentralGoogle Scholar
  147. 147.
    Ireland SJ, Guzman AA, O’Brien DE, Hughes S, Greenberg B, Flores A, et al. The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remitting multiple sclerosis. JAMA Neurol. 2014;71(11):1421–8.PubMedPubMedCentralGoogle Scholar
  148. 148.
    Hong J, Li N, Zhang X, Zheng B, Zhang JZ. Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3. Proc Natl Acad Sci U S A. 2005;102(18):6449–54.PubMedPubMedCentralGoogle Scholar
  149. 149.
    Kuerten S, Jackson LJ, Kaye J, Vollmer TL. Impact of glatiramer acetate on B cell-mediated pathogenesis of multiple sclerosis. CNS Drugs. 2018;32(11):1039–51.PubMedPubMedCentralGoogle Scholar
  150. 150.
    Farina C, Weber MS, Meinl E, Wekerle H, Hohlfeld R. Glatiramer acetate in multiple sclerosis: update on potential mechanisms of action. Lancet Neurol. 2005;4(9):567–75.PubMedPubMedCentralGoogle Scholar
  151. 151.
    Ruggieri M, Avolio C, Livrea P, Trojano M. Glatiramer acetate in multiple sclerosis: a review. CNS Drug Rev. 2007;13(2):178–91.PubMedPubMedCentralGoogle Scholar
  152. 152.
    Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335(1):2–13.PubMedPubMedCentralGoogle Scholar
  153. 153.
    Buttgereit F, Wehling M, Burmester GR. A new hypothesis of modular glucocorticoid actions: steroid treatment of rheumatic diseases revisited. Arthritis Rheum. 1998;41(5):761–7.PubMedGoogle Scholar
  154. 154.
    Liberman AC, Budziñski ML, Sokn C, Gobbini RP, Steininger A, Arzt E. Regulatory and mechanistic actions of glucocorticoids on T and inflammatory cells. Front Endocrinol. 2018;9:235.Google Scholar
  155. 155.
    Barnes PJ. Molecular mechanisms and cellular effects of glucocorticosteroids. Immunol Allergy Clin N Am. 2005;25(3):451–68.Google Scholar
  156. 156.
    Cronstein BN, Kimmel SC, Levin RI, Martiniuk F, Weissmann G. A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1992;89(21):9991–5.PubMedPubMedCentralGoogle Scholar
  157. 157.
    Leussink VI, Jung S, Merschdorf U, Toyka KV, Gold R. High-dose methylprednisolone therapy in multiple sclerosis induces apoptosis in peripheral blood leukocytes. Arch Neurol. 2001;58(1):91–7.PubMedGoogle Scholar
  158. 158.
    Zhang J, Hutton G, Zang Y. A comparison of the mechanisms of action of interferon beta and glatiramer acetate in the treatment of multiple sclerosis. Clin Ther. 2002;24(12):1998–2021.PubMedGoogle Scholar
  159. 159.
    Kieseier BC. The mechanism of action of interferon-β in relapsing multiple sclerosis. CNS Drugs. 2011;25(6):491–502.PubMedGoogle Scholar
  160. 160.
    Kavrochorianou N, Markogiannaki M, Haralambous S. IFN-β differentially regulates the function of T cell subsets in MS and EAE. Cytokine Growth Factor Rev. 2016;30:47–54.PubMedGoogle Scholar
  161. 161.
    Wang K-C, Lin K-H, Lee T-C, Lee C-L, Chen S-Y, Chen S-J, et al. Poor responses to interferon-beta treatment in patients with neuromyelitis optica and multiple sclerosis with long spinal cord lesions. PLoS One. 2014;9(6):e98192.PubMedPubMedCentralGoogle Scholar
  162. 162.
    Palace J, Leite MI, Nairne A, Vincent A. Interferon Beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers. Arch Neurol. 2010;67(8):1016–7.PubMedGoogle Scholar
  163. 163.
    Cherin P, Marie I, Michallet M, Pelus E, Dantal J, Crave J-C, et al. Management of adverse events in the treatment of patients with immunoglobulin therapy: a review of evidence. Autoimmun Rev. 2016;15(1):71–81.PubMedGoogle Scholar
  164. 164.
    Bittner B, Richter W, Schmidt J. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities. BioDrugs. 2018;32(5):425–40.PubMedPubMedCentralGoogle Scholar
  165. 165.
    Patwa HS, Chaudhry V, Katzberg H, Rae-Grant AD, So YT. Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the therapeutics and technology assessment Subcommittee of the American Academy of neurology. Neurology. 2012;78(13):1009–15.PubMedGoogle Scholar
  166. 166.
    Hughes RAC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2014;(9):CD002063.Google Scholar
  167. 167.
    Lancaster E. The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol. 2016;12(1):1–13.Google Scholar
  168. 168.
    Winkelmann A, Rommer PS, Hecker M, Zettl UK. Intravenous immunoglobulin treatment in multiple sclerosis: a prospective, rater-blinded analysis of relapse rates during pregnancy and the postnatal period. CNS Neurosci Ther. 2019;25(1):78–85.PubMedGoogle Scholar
  169. 169.
    Lünemann JD, Nimmerjahn F, Dalakas MC. Intravenous immunoglobulin in neurology--mode of action and clinical efficacy. Nat Rev Neurol. 2015;11(2):80–9.PubMedGoogle Scholar
  170. 170.
    Janke AD, Yong VW. Impact of IVIg on the interaction between activated T cells and microglia. Neurol Res. 2006;28(3):270–4.PubMedGoogle Scholar
  171. 171.
    Lünemann JD, Quast I, Dalakas MC. Efficacy of intravenous immunoglobulin in neurological diseases. Neurotherapeutics. 2016;13(1):34–46.PubMedGoogle Scholar
  172. 172.
    Vollmer T, Stewart T, Baxter N. Mitoxantrone and cytotoxic drugs’ mechanisms of action. Neurology. 2010;74(Suppl 1):S41–6.PubMedGoogle Scholar
  173. 173.
    Thomas X, Archimbaud E. Mitoxantrone in the treatment of acute myelogenous leukemia: a review. Hematol Cell Ther. 1997;39(4):63–74.PubMedGoogle Scholar
  174. 174.
    Chan A, Weilbach FX, Toyka KV, Gold R. Mitoxantrone induces cell death in peripheral blood leucocytes of multiple sclerosis patients. Clin Exp Immunol. 2005;139(1):152–8.PubMedPubMedCentralGoogle Scholar
  175. 175.
    Neuhaus O, Wiendl H, Kieseier BC, Archelos JJ, Hemmer B, Stüve O, et al. Multiple sclerosis: mitoxantrone promotes differential effects on immunocompetent cells in vitro. J Neuroimmunol. 2005;168(1–2):128–37.PubMedGoogle Scholar
  176. 176.
    Kopadze T, Dehmel T, Hartung H-P, Stüve O, Kieseier BC. Inhibition by mitoxantrone of in vitro migration of immunocompetent cells: a possible mechanism for therapeutic efficacy in the treatment of multiple sclerosis. Arch Neurol. 2006;63(11):1572–8.PubMedGoogle Scholar
  177. 177.
    Putzki N, Kumar M, Kreuzfelder E, Grosse-Wilde H, Diener HC, Limmroth V. Mitoxantrone does not restore the impaired suppressive function of natural regulatory T cells in patients suffering from multiple sclerosis. A longitudinal ex vivo and in vitro study. Eur Neurol. 2009;61(1):27–32.PubMedGoogle Scholar
  178. 178.
    Kingwell E, Koch M, Leung B, Isserow S, Geddes J, Rieckmann P, et al. Cardiotoxicity and other adverse events associated with mitoxantrone treatment for MS. Neurology. 2010;74(22):1822–6.PubMedPubMedCentralGoogle Scholar
  179. 179.
    Cocco E, Marrosu MG. The current role of mitoxantrone in the treatment of multiple sclerosis. Expert Rev Neurother. 2014;14(6):607–16.PubMedGoogle Scholar
  180. 180.
    Research C for DE and. Postmarket drug safety information for patients and providers – mitoxantrone hydrochloride (marketed as Novantrone and generics) – Healthcare Professional Sheet text version [Internet]. [cited 2018 Nov 14]. Available from: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126445.htm
  181. 181.
    Xiong W, Lahita RG. Pragmatic approaches to therapy for systemic lupus erythematosus. Nat Rev Rheumatol. 2014;10(2):97–107.PubMedGoogle Scholar
  182. 182.
    Staatz CE, Tett SE. Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update. Arch Toxicol. 2014;88(7):1351–89.PubMedGoogle Scholar
  183. 183.
    Ginzler EM, Aranow C. Mycophenolate mofetil in lupus nephritis. Lupus. 2005;14(1):59–64.PubMedGoogle Scholar
  184. 184.
    Felten R, Scher F, Sibilia J, Chasset F, Arnaud L. Advances in the treatment of systemic lupus erythematosus: from back to the future, to the future and beyond. Joint Bone Spine. 2018. pii: S1297-319X(18)30304-X.Google Scholar
  185. 185.
    Villarroel MC, Hidalgo M, Jimeno A. Mycophenolate mofetil: an update. Drugs Today (Barc). 2009;45(7):521–32.Google Scholar
  186. 186.
    Gotterer L, Li Y. Maintenance immunosuppression in myasthenia gravis. J Neurol Sci. 2016;369:294–302.PubMedGoogle Scholar
  187. 187.
    Stüve O, Cravens PD, Frohman EM, Phillips JT, Remington GM, von Geldern G, et al. Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology. 2009;72(5):396–401.PubMedPubMedCentralGoogle Scholar
  188. 188.
    Stüve O, Marra CM, Bar-Or A, Niino M, Cravens PD, Cepok S, et al. Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. Arch Neurol. 2006;63(10):1383–7.PubMedGoogle Scholar
  189. 189.
    Pagnini C, Arseneau KO, Cominelli F. Natalizumab in the treatment of Crohn’s disease patients. Expert Opin Biol Ther. 2017;17(11):1433–8.PubMedGoogle Scholar
  190. 190.
    Tsokos GC, Balow JE. Immunosuppressive agents and plasmapheresis in immunological disorders. J Immunopharmacol. 1985;7(1):1–15.PubMedGoogle Scholar
  191. 191.
    Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the therapeutics and technology assessment Subcommittee of the American Academy of neurology. Neurology. 2011;76(3):294–300.PubMedPubMedCentralGoogle Scholar
  192. 192.
    Gwathmey K, Balogun RA, Burns T. Neurologic indications for therapeutic plasma exchange: 2011 update. J Clin Apher. 2012;27(3):138–45.PubMedGoogle Scholar
  193. 193.
    Lazaridis K, Dalianoudis I, Baltatzidi V, Tzartos SJ. Specific removal of autoantibodies by extracorporeal immunoadsorption ameliorates experimental autoimmune myasthenia gravis. J Neuroimmunol. 2017;312:24–30.PubMedGoogle Scholar
  194. 194.
    Faissner S, Nikolayczik J, Chan A, Hellwig K, Gold R, Yoon M-S, et al. Plasmapheresis and immunoadsorption in patients with steroid refractory multiple sclerosis relapses. J Neurol. 2016;263(6):1092–8.PubMedGoogle Scholar
  195. 195.
    Miller AE. Oral teriflunomide in the treatment of relapsing forms of multiple sclerosis: clinical evidence and long-term experience. Ther Adv Neurol Disord. 2017;10(12):381–96.PubMedPubMedCentralGoogle Scholar
  196. 196.
    Wostradowski T, Prajeeth CK, Gudi V, Kronenberg J, Witte S, Brieskorn M, et al. In vitro evaluation of physiologically relevant concentrations of teriflunomide on activation and proliferation of primary rodent microglia. J Neuroinflammation. 2016;13(1):250.PubMedPubMedCentralGoogle Scholar
  197. 197.
    Manna SK, Aggarwal BB. Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. J Immunol. 1999;162(4):2095–102.PubMedGoogle Scholar
  198. 198.
    González-Alvaro I, Ortiz AM, Domínguez-Jiménez C, Aragón-Bodi A, Díaz Sánchez B, Sánchez-Madrid F. Inhibition of tumour necrosis factor and IL-17 production by leflunomide involves the JAK/STAT pathway. Ann Rheum Dis. 2009;68(10):1644–50.PubMedGoogle Scholar
  199. 199.
    Groh J, Hörner M, Martini R. Teriflunomide attenuates neuroinflammation-related neural damage in mice carrying human PLP1 mutations. J Neuroinflammation. 2018;15(1):194.PubMedPubMedCentralGoogle Scholar
  200. 200.
    Araki M. Blockade of IL-6 signaling in neuromyelitis optica. Neurochem Int. 2018. pii: S0197-0186(18)30358-9.Google Scholar
  201. 201.
    Zola H, Flego L. Expression of interleukin-6 receptor on blood lymphocytes without in vitro activation. Immunology. 1992;76(2):338–40.PubMedPubMedCentralGoogle Scholar
  202. 202.
    Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages. Comparison with the expression in human hepatocytes. J Exp Med. 1989;170(5):1537–49.Google Scholar
  203. 203.
    Wu T-C, Chiang C-Y, Chan J-S, Lee C-Y, Leu H-B, Huang P-H, et al. Tocilizumab, a humanized monoclonal antibody against the interleukin-6 receptor, inhibits high glucose-induced vascular smooth muscle cell migration through mitogen-activated protein kinase signaling pathways. J Interf Cytokine Res. 2018;38(11):510–6.Google Scholar
  204. 204.
    Lin J, Xue B, Li X, Xia J. Monoclonal antibody therapy for neuromyelitis optica spectrum disorder: current and future. Int J Neurosci. 2017;127(8):735–44.PubMedGoogle Scholar
  205. 205.
    Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, et al. Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A. 2011;108(9):3701–6.PubMedPubMedCentralGoogle Scholar
  206. 206.
    Araki M, Matsuoka T, Miyamoto K, Kusunoki S, Okamoto T, Murata M, et al. Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology. 2014;82(15):1302–6.PubMedPubMedCentralGoogle Scholar
  207. 207.
    Ringelstein M, Ayzenberg I, Harmel J, Lauenstein A-S, Lensch E, Stögbauer F, et al. Long-term therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol. 2015;72(7):756–63.Google Scholar
  208. 208.
    Villiger PM, Adler S, Kuchen S, Wermelinger F, Dan D, Fiege V, et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387(10031):1921–7.PubMedGoogle Scholar
  209. 209.
    Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377(4):317–28.PubMedGoogle Scholar
  210. 210.
    Cogollo E, Cogollo E, Silva MA, Isenberg D. Profile of atacicept and its potential in the treatment of systemic lupus erythematosus. Drug Des Devel Ther. 2015;9:1331–9.PubMedPubMedCentralGoogle Scholar
  211. 211.
    Harvey PR, Gordon C. B-cell targeted therapies in systemic lupus erythematosus: successes and challenges. BioDrugs. 2013;27(2):85–95.PubMedGoogle Scholar
  212. 212.
    Kappos L, Hartung H-P, Freedman MS, Boyko A, Radü EW, Mikol DD, et al. Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol. 2014;13(4):353–63.PubMedGoogle Scholar
  213. 213.
    Vigolo M, Chambers MG, Willen L, Chevalley D, Maskos K, Lammens A, et al. A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors. Nat Commun. 2018;9(1):1199.PubMedPubMedCentralGoogle Scholar
  214. 214.
    Stohl W, Hiepe F, Latinis KM, Thomas M, Scheinberg MA, Clarke A, et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64(7):2328–37.PubMedPubMedCentralGoogle Scholar
  215. 215.
    Hewett K, Sanders DB, Grove RA, Broderick CL, Rudo TJ, Bassiri A, et al. Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis. Neurology. 2018;90(16):e1425–34.PubMedPubMedCentralGoogle Scholar
  216. 216.
    Guptill JT, Soni M, Meriggioli MN. Current treatment, emerging translational therapies, and new therapeutic targets for autoimmune myasthenia gravis. Neurotherapeutics. 2016;13(1):118–31.PubMedGoogle Scholar
  217. 217.
    Schneider-Gold C, Reinacher-Schick A, Ellrichmann G, Gold R. Bortezomib in severe MuSK-antibody positive myasthenia gravis: first clinical experience. Ther Adv Neurol Disord. 2017;10(10):339–41.PubMedPubMedCentralGoogle Scholar
  218. 218.
    Scheibe F, Prüss H, Mengel AM, Kohler S, Nümann A, Köhnlein M, et al. Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology. 2017;88(4):366–70.PubMedGoogle Scholar
  219. 219.
    Musette P, Bouaziz JD. B cell modulation strategies in autoimmune diseases: new concepts. Front Immunol [Internet]. 2018 [cited 2018 Nov 5];9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908887/
  220. 220.
    Roopenian DC, Akilesh S. FcRn: the neonatal fc receptor comes of age. Nat Rev Immunol. 2007;7(9):715–25.PubMedGoogle Scholar
  221. 221.
    Kaplon H, Reichert JM. Antibodies to watch in 2018. MAbs. 2018;10(2):183–203.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of NeurologyMedical University of ViennaViennaAustria
  2. 2.Department of NeurologyNeuroimmunological Section, University of RostockRostockGermany

Personalised recommendations