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Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside

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Abstract

Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibody-mediated, inflammatory demyelinating disease of the central nervous system, characterized by optic neuritis and transverse myelitis. The binding of NMO-IgG with astrocytic aquaporin-4 (AQP4) functions directly in the pathogenesis of >60% of NMOSD patients, and causes astrocyte loss, secondary inflammatory infiltration, demyelination, and neuron death, potentially leading to paralysis and blindness. Current treatment options, including immunosuppressive agents, plasma exchange, and B-cell depletion, are based on small retrospective case series and open-label studies. It is noteworthy that monoclonal antibody (mAb) therapy is a better option for autoimmune diseases due to its high efficacy and tolerability. Although the pathophysiological mechanisms of NMOSD remain unknown, increasingly, therapeutic studies have focused on mAbs, which target B cell depletion, complement and inflammation cascade inactivation, blood-brain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy of mAb trials in NMOSD, including preclinical and experimental investigations.

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References

  1. Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007, 6: 805–815.

    PubMed  CAS  Google Scholar 

  2. Jacob A, McKeon A, Nakashima I, Sato DK, Elsone L, Fujihara K, et al. Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders. J Neurol Neurosurg Psychiatry 2013, 84: 922–930.

    PubMed  Google Scholar 

  3. Jarius S, Paul F, Franciotta D, Waters P, Zipp F, Hohlfeld R, et al. Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica. Nat Clin Pract Neurol 2008, 4: 202–214.

    PubMed  CAS  Google Scholar 

  4. 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: 2106–2112.

    PubMed  CAS  Google Scholar 

  5. Kleiter I. Failure of natalizumab to prevent relapses in neuromyelitis optica. Arch Neurol 2012, 69: 239.

    PubMed  Google Scholar 

  6. 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: 1016–1017.

    PubMed  Google Scholar 

  7. Hinson SR, Pittock SJ, Lucchinetti CF, Roemer SF, Fryer JP, Kryzer TJ, et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 2007, 69: 2221–2231.

    PubMed  CAS  Google Scholar 

  8. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 2005, 202: 473–477.

    PubMed  PubMed Central  CAS  Google Scholar 

  9. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015, 85: 177–189.

    PubMed  PubMed Central  Google Scholar 

  10. Bradl M, Reindl M, Lassmann H. Mechanisms for lesion localization in neuromyelitis optica spectrum disorders. Curr Opin Neurol 2018, 31: 325.

    PubMed  PubMed Central  Google Scholar 

  11. Hamid SHM, Whittam D, Mutch K, Linaker S, Solomon T, Das K, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol 2017, 264: 2088–2094.

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Sato DK. Distinction between MOG antibody- positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014, 82: 474–481.

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Sepúlveda M, Aldea M, Escudero D, Llufriu S, Arrambide G, Otero-Romero S, et al. Epidemiology of NMOSD in Catalonia: Influence of the new 2015 criteria in incidence and prevalence estimates. Mult Scler J 2017, 24, 1843-1851.

    Google Scholar 

  14. Yan Y, Li Y, Fu Y, Yang L, Su L, Shi K, et al. Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD. Sci China Life Sci 2016, 59: 1270–1281.

    PubMed  PubMed Central  CAS  Google Scholar 

  15. Alves Do Rego C, Collongues N. Neuromyelitis optica spectrum disorders: Features of aquaporin-4, myelin oligodendrocyte glycoprotein and double-seronegative-mediated subtypes. Rev Neurol 2018, 174: 458–470.

    PubMed  CAS  Google Scholar 

  16. Durozard P, Rico A, Boutiere C, Maarouf A, Lacroix R, Cointe S, et al. Comparison of the response to rituximab between myelin oligodendrocyte glycoprotein and aquaporin‐4 antibody diseases. Ann Neurol 2020, 87: 256–266.

    PubMed  CAS  Google Scholar 

  17. Kitley J, Woodhall M, Waters P, Leite MI, Devenney E, Craig J, et al. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology 2012, 79: 1273–1277.

    PubMed  CAS  Google Scholar 

  18. Kezuka T, Usui Y, Yamakawa N, Matsunaga Y, Matsuda R, Masuda M, et al. Relationship between NMO-antibody and anti–MOG antibody in optic neuritis. J Neuroophthalmol 2012, 32: 107–110.

    PubMed  Google Scholar 

  19. Hamid SHM, Whittam D, Saviour M, Alorainy A, Mutch K, Linaker S, et al. Seizures and encephalitis in myelin oligodendrocyte glycoprotein IgG disease vs aquaporin 4 IgG disease. JAMA Neurol 2018, 75: 65–71.

    PubMed  Google Scholar 

  20. Ungureanu A, de Seze J, Ahle G, Sellal F. Myelin oligodendrocyte glycoprotein antibodies in neuromyelitis optica spectrum disorder. Rev Neurol 2018, 01: 378–383.

    Google Scholar 

  21. Fang L. Myelin oligodendrocyte glycoprotein-IgG contributes to oligodendrocytopathy in the presence of complement, distinct from astrocytopathy induced by AQP4-IgG. Neurosci Bull 2019, 35: 853–866.

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Bove R, Elsone L, Alvarez E, Borisow N, Cortez MM, Mateen FJ, et al. Female hormonal exposures and neuromyelitis optica symptom onset in a multicenter study. Neuroinflammation 2017, 4: e339.

    Google Scholar 

  23. Flanagan EP, Cabre P, Weinshenker BG, Sauver JS, Jacobson DJ, Majed M, et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum: Aquaporin-4-IgG Seroprevalence. Ann Neurol 2016, 79: 775–783.

    PubMed  PubMed Central  CAS  Google Scholar 

  24. Jarius S, Ruprecht K, Wildemann B, Kuempfel T, Ringelstein M, Geis C, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients. J Neuroinflammation 2012, 9: 14.

    PubMed  PubMed Central  CAS  Google Scholar 

  25. Banwell B, Tenembaum S, Lennon VA, Ursell E, Kennedy J, Bar-Or A, et al. Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders. Neurology 2008, 70: 344–352.

    PubMed  CAS  Google Scholar 

  26. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999, 53: 1107–1114.

    PubMed  CAS  Google Scholar 

  27. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology 2003, 60: 848–853.

    PubMed  Google Scholar 

  28. 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 2007, 130: 1235–1243.

    PubMed  Google Scholar 

  29. Miyazaki K, Abe Y, Iwanari H, Suzuki Y, Kikuchi T, Ito T, et al. Establishment of monoclonal antibodies against the extracellular domain that block binding of NMO-IgG to AQP4. J Neuroimmunol 2013, 260: 107–116.

    PubMed  CAS  Google Scholar 

  30. Phuan PW, Anderson MO, Tradtrantip L, Zhang H, Tan J, Lam C, et al. A small-molecule screen yields idiotype-specific blockers of neuromyelitis optica immunoglobulin G binding to aquaporin-4. J Biol Chem 2012, 287: 36837–36844.

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Tradtrantip L, Zhang H, Anderson MO, Saadoun S, Phuan PW, Papadopoulos MC, et al. Small-molecule inhibitors of NMO-IgG binding to aquaporin-4 reduce astrocyte cytotoxicity in neuromyelitis optica. FASEB J 2012, 26: 2197–2208.

    PubMed  PubMed Central  CAS  Google Scholar 

  32. Tradtrantip L, Asavapanumas N, Verkman AS. Therapeutic cleavage of anti-aquaporin-4 autoantibody in neuromyelitis optica by an IgG-selective proteinase. Mol Pharmacol 2013, 83: 1268–1275.

    PubMed  PubMed Central  CAS  Google Scholar 

  33. Leavitt J. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Yearb Neurol Neurosurg 2009, 2009: 112–113.

    Google Scholar 

  34. Miyamoto K, Kusunoki S. Intermittent plasmapheresis prevents recurrence in neuromyelitis optica. Ther Apher Dial 2009, 13: 505–508.

    PubMed  Google Scholar 

  35. Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol 2014, 10: 493–506.

    PubMed  PubMed Central  CAS  Google Scholar 

  36. Kim SH, Kim W, Huh SY, Lee KY, Jung IJ, Kim HJ. Clinical efficacy of plasmapheresis in patients with neuromyelitis optica spectrum disorder and effects on circulating anti-aquaporin-4 antibody levels. J Clin Neurol 2013, 9: 36–42.

    PubMed  PubMed Central  Google Scholar 

  37. Van Herle K, Behne JM, Van Herle A, Blaschke TF, Smith TJ, Yeaman MR. Integrative continuum: accelerating therapeutic advances in rare autoimmune diseases. Annu Rev Pharmacol Toxicol 2012, 52: 523–547.

    PubMed  Google Scholar 

  38. Klotz L, Wiendl H. Monoclonal antibodies in neuroinflammatory diseases. Expert Opin Biol Ther 2013, 13: 831–846.

    PubMed  CAS  Google Scholar 

  39. 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: 1302–1306.

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Tradtrantip L, Zhang H, Saadoun S, Phuan PW, Lam C, Papadopoulos MC, et al. Anti-Aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica. Ann Neurol 2012, 71: 314–322.

    PubMed  PubMed Central  CAS  Google Scholar 

  41. Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Biotechnology 1975, 24: 524.

    Google Scholar 

  42. Tjandra JJ, Ramadi L, McKenzie IFC. Development of human anti-murine antibody (HAMA) response in patients. Immunol Cell Biol 1990, 68: 367–376.

    PubMed  Google Scholar 

  43. Hwang WYK, Foote J. Immunogenicity of engineered antibodies. Methods 2005, 36: 3–10.

    PubMed  CAS  Google Scholar 

  44. Presta LG. Engineering of therapeutic antibodies to minimize immunogenicity and optimize function. Adv Drug Deliv Rev 2006, 58: 640–656.

    PubMed  CAS  Google Scholar 

  45. Jespers LS, Roberts A, Mahler SM, Winter G, Hoogenboom HR. Guiding the selection of human antibodies from phage display repertoires to a single epitope of an antigen. Biotechnology 1994, 12: 899.

    PubMed  CAS  Google Scholar 

  46. Zéphir H, Bernard-Valnet R, Lebrun C, Outteryck O, Audoin B, Bourre B, et al. Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability. J Neurol 2015, 262: 2329–2335.

    PubMed  Google Scholar 

  47. Le GTM, Herbi L, De RC, Nguyen-Khac F, Davi F, Grelier A, et al. Antibody-dependent cellular cytotoxicity of the optimized anti-CD20 monoclonal antibody ublituximab on chronic lymphocytic leukemia cells with the 17p deletion. Leukemia 2014, 28: 230–233.

    Google Scholar 

  48. Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol 2013, 12: 554–562.

    PubMed  CAS  Google Scholar 

  49. Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T. Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Mod Rheumatol 2013, 23: 827–831.

    PubMed  CAS  Google Scholar 

  50. Mealy MA, Shin K, John G, Levy M. Bevacizumab is safe in acute relapses of neuromyelitis optica. Clin Exp Neuroimmunol 2015, 6: 413–418.

    PubMed  PubMed Central  CAS  Google Scholar 

  51. Taylor RP, Lindorfer MA. Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies. Curr Opin Immunol 2008, 20: 444–449.

    PubMed  PubMed Central  CAS  Google Scholar 

  52. Bennett JL, Lam C, Kalluri SR, Saikali P, Bautista K, Dupree C, et al. Intrathecal pathogenic anti–aquaporin-4 antibodies in early neuromyelitis optica. Ann Neurol 2009, 66: 617–629.

    PubMed  PubMed Central  CAS  Google Scholar 

  53. Hohlfeld R. B-cells as therapeutic targets in neuro-inflammatory diseases. Clin Immunol 2018, 186: 51–53.

    PubMed  CAS  Google Scholar 

  54. Hinson SR, McKeon A, Fryer JP, Apiwattanakul M, Lennon VA, Pittock SJ. Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4–expressing cells. Arch Neurol 2009, 66: 1164-1167.

    PubMed  Google Scholar 

  55. Ratelade J, Zhang H, Saadoun S, Bennett JL, Papadopoulos MC, Verkman AS. Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss. Acta Neuropathol 2012, 123: 861–872.

    PubMed  PubMed Central  CAS  Google Scholar 

  56. Monson NL, Cravens PD, Frohman EM, Hawker K, Racke MK. 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  Google Scholar 

  57. Rastetter W, Molina A, White CA. Rituximab: Expanding role in therapy for lymphomas and autoimmune diseases. Annu Rev Med 2004, 55: 477–503.

    PubMed  CAS  Google Scholar 

  58. Dalakas MC. B cells as therapeutic targets in autoimmune neurological disorders. Nat Clin Pract Neurol 2008, 4: 557–567.

    PubMed  CAS  Google Scholar 

  59. Graves J, Vinayagasundaram U, Mowry EM, Matthews IR, Marino JA, Cheng J, et al. Effects of rituximab on lymphocytes in multiple sclerosis and neuromyelitis optica. Mult Scler Relat Disord 2014, 3: 244–252.

    PubMed  Google Scholar 

  60. Wilk E, Witte T, Marquardt N, Horvath T, Kalippke K, Scholz K, et al. Depletion of functionally active CD20+ T cells by rituximab treatment. Arthritis Rheum 2009, 60: 3563–3571.

    PubMed  CAS  Google Scholar 

  61. Yang CS. Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis. Optica 2013, 81: 710–713.

    CAS  Google Scholar 

  62. Edwards JCW, Szechinski J, Emery P, Shaw T. Efficacy of B-cell–targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 2004, 350: 2572–2581.

    PubMed  CAS  Google Scholar 

  63. Hauser SL, Arnold DL, Fox RJ, Sarkar N, Smith CH. B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. N Engl J Med 2008, 358: 676–688.

    PubMed  CAS  Google Scholar 

  64. Reske D, Haupt WF. Use of rituximab in multiple sclerosis: current progress and future perspectives. Expert Rev Clin Immunol 2008, 4: 573–582.

    PubMed  CAS  Google Scholar 

  65. Salvi M, Vannucchi G, Campi I, Beck-Peccoz P. Rituximab in the treatment of thyroid eye disease: science fiction? Orbit 2009, 28: 251–255.

    PubMed  Google Scholar 

  66. Cree BA, Lamb S, Morgan K, Chen A, Waubant E, Genain C. An open label study of the effects of rituximab in neuromyelitis optica. Neurology 2005, 64: 1270–1272.

    PubMed  CAS  Google Scholar 

  67. Bedi GS, Brown AD, Delgado SR, Usmani N, Lam BL, Sheremata WA. Impact of rituximab on relapse rate and disability in neuromyelitis optica. Mult Scler J 2011, 17: 1225–1230.

    CAS  Google Scholar 

  68. Collongues N, Brassat D, Maillart E, Labauge P, Ouallet J, Carra-Dalliere C, et al. Efficacy of rituximab in refractory neuromyelitis optica. Mult Scler J 2016, 22: 955–959.

    CAS  Google Scholar 

  69. Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol 2013, 70: 1110–1117.

    PubMed  Google Scholar 

  70. Memon AB, Javed A, Caon C, Srivastawa S, Bao F, Bernitsas E, et al. Long-term safety of rituximab induced peripheral B-cell depletion in autoimmune neurological diseases. PLoS One 2018, 13: e0190425.

    PubMed  PubMed Central  Google Scholar 

  71. Nikoo Z, Badihian S, Shaygannejad V, Asgari N, Ashtari F. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial. J Neurol 2017, 264: 2003–2009.

    PubMed  CAS  Google Scholar 

  72. Ciron J, Audoin B, Bourre B, Brassat D, Durand-Dubief F, Laplaud D, et al. Recommendations for the use of Rituximab in neuromyelitis optica spectrum disorders. Rev Neurol 2018, 174: 255–264.

    PubMed  CAS  Google Scholar 

  73. Carson KR, Focosi D, Major EO, Petrini M, Richey EA, West DP, et al. Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a Review from the Research on Adverse Drug Events and Reports (RADAR) Project. Lancet Oncol 2009, 10: 816–824.

    PubMed  CAS  Google Scholar 

  74. Clifford DB. Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol 2011, 68: 1156–1164.

    PubMed  PubMed Central  Google Scholar 

  75. Tsutsumi Y. Hepatitis B virus reactivation with a rituximab-containing regimen. World J Hepatol 2015, 7: 2344.

    PubMed  PubMed Central  Google Scholar 

  76. Sharman JP, Farber CM, Mahadevan D, Schreeder MT, Brooks HD, Kolibaba KS, et al. Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial. Br J Haematol 2017, 176: 412–420.

    PubMed  CAS  Google Scholar 

  77. Konno Y, Kobayashi Y, Takahashi K, Takahashi E, Sakae S, Wakitani M, et al. Fucose content of monoclonal antibodies can be controlled by culture medium osmolality for high antibody-dependent cellular cytotoxicity. Cytotechnology 2012, 64: 249–265.

    PubMed  CAS  Google Scholar 

  78. Agius MA, Klodowska-Duda G, Maciejowski M, Potemkowski A, Li J, Patra K, et al. Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study. Mult Scler 2017, 25: 235–245.

    PubMed  PubMed Central  Google Scholar 

  79. Tedder TF. CD19: a promising B cell target for rheumatoid arthritis. Nat Rev Rheumatol 2009, 5: 572–577.

    PubMed  CAS  Google Scholar 

  80. Schuh E, Berer K, Mulazzani M, Feil K, Meinl I, Lahm H, et al. Features of human CD3+ CD20+ T cells. J Immunol 2016, 197: 1111–1117.

    PubMed  CAS  Google Scholar 

  81. Palanichamy A, Jahn S, Nickles D, Derstine M, Abounasr A, Hauser SL, et al. Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J Immunol 2014, 193: 580–586.

    PubMed  PubMed Central  CAS  Google Scholar 

  82. Hammer O. CD19 as an attractive target for antibody-based therapy. mAbs 2012, 4: 571–577.

    PubMed  PubMed Central  Google Scholar 

  83. Schiopu E, Chatterjee S, Hsu V, Flor A, Cimbora D, Patra K, et al. Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study. Arthritis Res Ther 2016, 18: 131.

    PubMed  PubMed Central  Google Scholar 

  84. Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 2019, 394: 1352–1363.

    PubMed  CAS  Google Scholar 

  85. Stüve O, Warnke C, Deason K, Stangel M, Kieseier BC, Hartung HP, et al. CD19 as a molecular target in CNS autoimmunity. Acta Neuropathol 2014, 128: 177–190.

    PubMed  PubMed Central  Google Scholar 

  86. 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: 1256–1264.

    PubMed  CAS  Google Scholar 

  87. Hengstman GJD, Wesseling P, Frenken CWGM, Jongen PJH. Neuromyelitis optica with clinical and histopathological involvement of the brain. Mult Scler J 2007, 13: 679–682.

    CAS  Google Scholar 

  88. Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain 2010, 133: 349–361.

    PubMed  PubMed Central  Google Scholar 

  89. Zhang H, Bennett JL, Verkman AS. Ex vivo spinal cord slice model of neuromyelitis optica reveals novel immunopathogenic mechanisms. Ann Neurol 2011, 70: 943–954.

    PubMed  PubMed Central  CAS  Google Scholar 

  90. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol 2010, 11: 785–797.

    PubMed  PubMed Central  CAS  Google Scholar 

  91. Ricklin D, Lambris JD. Complement-targeted therapeutics. Nat Biotechnol 2007, 25: 1265–1275.

    PubMed  PubMed Central  CAS  Google Scholar 

  92. Jore MM, Johnson S, Sheppard D, Barber NM, Li YI, Nunn MA, et al. Structural basis for therapeutic inhibition of complement C5. Nat Struct Mol Biol 2016, 23: 378–386.

    PubMed  PubMed Central  CAS  Google Scholar 

  93. Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, et al. Eculizumab in aquaporin-4–positive neuromyelitis optica spectrum disorder. N Engl J Med 2019, 381: 614–625.

    PubMed  CAS  Google Scholar 

  94. Tanaka T, Narazaki M, Kishimoto T. Therapeutic targeting of the interleukin-6 receptor. Annu Rev Pharmacol Toxicol 2012, 52: 199–219.

    PubMed  CAS  Google Scholar 

  95. 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: 3701–3706.

    PubMed  PubMed Central  CAS  Google Scholar 

  96. Uzawa A, Mori M, Sawai S, Masuda S, Muto M, Uchida T, et al. Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks. Clin Chim Acta 2013, 421: 181–183.

    PubMed  CAS  Google Scholar 

  97. Wang H, Wang K, Zhong X, Dai Y, Qiu W, Wu A, et al. Notable increased cerebrospinal fluid levels of soluble interleukin-6 receptors in neuromyelitis optica. Neuroimmunomodulation 2012, 19: 304–308.

    PubMed  Google Scholar 

  98. Kieseier BC, Stüve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, et al. Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses. JAMA Neurol 2013, 70: 390.

    PubMed  Google Scholar 

  99. Komai T, Shoda H, Yamaguchi K, Sakurai K, Shibuya M, Kubo K, et al. Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: A case report. Mod Rheumatol 2016, 26: 294–296.

    PubMed  Google Scholar 

  100. Araki M. Blockade of IL-6 signaling in neuromyelitis optica. Neurochem Int 2018, 2018: 104315.

    Google Scholar 

  101. 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: 756.

    PubMed  Google Scholar 

  102. Ayzenberg I, Kleiter I, Schröder A, Hellwig K, Chan A, Yamamura T, et al. Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol 2013, 70: 394–397.

    PubMed  Google Scholar 

  103. Qian P, Lancia S, Alvarez E, Klawiter EC, Cross AH, Naismith RT. Association of neuromyelitis optica with severe and intractable pain. Arch Neurol 2012, 69: 1482–1487.

    PubMed  PubMed Central  Google Scholar 

  104. Ohtori S, Miyagi M, Eguchi Y, Inoue G, Orita S, Ochiai N, et al. Efficacy of epidural administration of anti-interleukin-6 receptor antibody onto spinal nerve for treatment of sciatica. Eur Spine J 2012, 21: 2079–2084.

    PubMed  PubMed Central  Google Scholar 

  105. Beauchemin P, Carruthers R. MS arising during Tocilizumab therapy for rheumatoid arthritis. Mult Scler J 2016, 22: 254–256.

    CAS  Google Scholar 

  106. Gabay C, McInnes IB, Kavanaugh A, Tuckwell K, Klearman M, Pulley J, et al. Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis. Ann Rheum Dis 2016, 75: 1806–1812.

    PubMed  Google Scholar 

  107. Gout T, Östör AJK, Nisar MK. Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review. Clin Rheumatol 2011, 30: 1471–1474.

    PubMed  Google Scholar 

  108. Iwasa T, Nakamura K, Ogino H, Itaba S, Akiho H, Okamoto R, et al. Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis. Endoscopy 2011, 43: 70–72.

    PubMed  CAS  Google Scholar 

  109. Paul F, Murphy O, Pardo S, Levy M. Investigational drugs in development to prevent neuromyelitis optica relapses. Expert Opin Investig Drugs 2018, 27: 265–271.

    PubMed  CAS  Google Scholar 

  110. Kaplon H, Reichert JM. Antibodies to watch in 2018. mAbs 2018, 10: 183–203.

    PubMed  PubMed Central  CAS  Google Scholar 

  111. Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, et al. Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med 2019, 381: 2114–2124.

    PubMed  CAS  Google Scholar 

  112. Wang Y, Fei D, Vanderlaan M, Song A. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 2004, 7: 335–345.

    PubMed  CAS  Google Scholar 

  113. Shimizu F, Sano Y, Takahashi T, Haruki H, Saito K, Koga M, et al. Sera from neuromyelitis optica patients disrupt the blood–brain barrier. J Neurol Neurosurg Psychiatry 2012, 83: 288–297.

    PubMed  Google Scholar 

  114. Vincent T, Saikali P, Cayrol R, Roth AD, Bar-Or A, Prat A, et al. Functional consequences of neuromyelitis optica-igg astrocyte interactions on blood-brain barrier permeability and granulocyte recruitment. J Immunol 2008, 181: 5730–5737.

    PubMed  CAS  Google Scholar 

  115. Argaw AT, Gurfein BT, Zhang Y, Zameer A, John GR. VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci U S A 2009, 106: 1977–1982.

    PubMed  PubMed Central  CAS  Google Scholar 

  116. Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, et al. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest 2012, 122: 2454–2468.

    PubMed  PubMed Central  CAS  Google Scholar 

  117. Bradl M, Misu T, Takahashi T, Watanabe M, Mader S, Reindl M, et al. Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo. Ann Neurol 2009, 66: 630–643.

    PubMed  CAS  Google Scholar 

  118. Phuan PW, Zhang H, Asavapanumas N, Leviten M, Rosenthal A, Tradtrantip L, et al. C1q-targeted monoclonal antibody prevents complement-dependent cytotoxicity and neuropathology in in vitro and mouse models of neuromyelitis optica. Acta Neuropathol 2013, 125: 829–840.

    PubMed  PubMed Central  CAS  Google Scholar 

  119. Bourre B, Marignier R, Zephir H, Papeix C, Brassat D, Castelnovo G, et al. Neuromyelitis optica and pregnancy 2012, 78: 875–879.

    CAS  Google Scholar 

  120. Kim W, Kim S-H, Nakashima I, Takai Y, Fujihara K, Leite MI, et al. Influence of pregnancy on neuromyelitis optica spectrum disorder. Neurology 2012, 78: 1264–1267.

    PubMed  CAS  Google Scholar 

  121. Kimby E, Sverrisdottir A, Elinder G. Safety of rituximab therapy during the first trimester of pregnancy: a case history. Eur J Haematol 2004, 72: 292–295.

    PubMed  Google Scholar 

  122. Ojeda-Uribe M, Afif N, Dahan E, Sparsa L, Haby C, Sibilia J, et al. Exposure to abatacept or rituximab in the first trimester of pregnancy in three women with autoimmune diseases. Clin Rheumatol 2013, 32: 695–700.

    PubMed  Google Scholar 

  123. Ponte P, Lopes MJP. Apparent safe use of single dose rituximab for recalcitrant atopic dermatitis in the first trimester of a twin pregnancy. J Am Acad Dermatol 2010, 63: 355–356.

    PubMed  Google Scholar 

  124. Ringelstein M, Harmel J, Distelmaier F, Ingwersen J, Menge T, Hellwig K, et al. Neuromyelitis optica and pregnancy during therapeutic B cell depletion: infant exposure to anti-AQP4 antibody and prevention of rebound relapses with low-dose rituximab postpartum. Mult Scler J 2013, 19: 1544–1547.

    CAS  Google Scholar 

  125. Simister N. Placental transport of immunoglobulin G. Vaccine 2003, 21: 3365–3369.

    PubMed  CAS  Google Scholar 

  126. Das G, Damotte V, Gelfand JM, Bevan C, Cree BAC, Do L, et al. Rituximab before and during pregnancy: A systematic review, and a case series in MS and NMOSD. Neurol Neuroimmunol Neuroinflamm 2018, 5: e453.

    PubMed  PubMed Central  Google Scholar 

  127. Shi K, Wang Z, Liu Y, Gong Y, Fu Y, Li S, et al. CFHR1-modified neural stem cells ameliorated brain injury in a mouse model of neuromyelitis optica spectrum disorders. J Immunol 2016, 197: 3471–3480.

    PubMed  CAS  Google Scholar 

  128. Wang Z, Guo W, Liu Y, Gong Y, Ding X, Shi K, et al. Low expression of complement inhibitory protein CD59 contributes to humoral autoimmunity against astrocytes. Brain Behav Immun 2017, 65: 173–182.

    PubMed  CAS  Google Scholar 

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Acknowledgements

This review was supported by the National Natural Science Foundation of China (81571596 and 81601044), the National Key R&D Program of China (2017YFC1701300), and Fundamental Research Funds for the Central Universities, China (GK201701009).

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  1. Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi’an, 710119, China

    Wenli Zhu, Yaling Zhang, Zhen Wang, Ying Fu & Yaping Yan

  2. Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Wenli Zhu

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  1. Wenli Zhu
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Correspondence to Yaping Yan.

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Zhu, W., Zhang, Y., Wang, Z. et al. Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside. Neurosci. Bull. 36, 1213–1224 (2020). https://doi.org/10.1007/s12264-020-00525-3

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