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Cited by 262Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersOcular Diseases and Behçet’s Syndrome

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

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Papadopoulos, Marios C., Bennett, Jeffrey L., Verkman, Alan S.·2014·Nature Reviews Neurology
DOI 10.1038/nrneurol.2014.141PMC PMC4229040
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Abstract

Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerve, and can lead to paralysis and blindness. Currently, several treatment options for NMO exist, but many have been adapted from multiple sclerosis, and no controlled clinical trials specific to NMO have been conducted to date. Here, Marios Papadopoulos and colleagues review the various treatment strategies in NMO, and discuss the drugs that are in development or could be repurposed to treat this condition. Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood–brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19—all initially developed for other indications—are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood–brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date.

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  1. [1]Lennon VA A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis Lancet 364 2106 2112 2004 15589308
  2. [2]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 202 473 477 2005 16087714 PMC2212860
  3. [3]Hinson SR Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica Neurology 69 2221 2231 2007 17928579
  4. [4]Wingerchuk DM Lennon VA Pittock SJ Lucchinetti CF Weinshenker BG Revised diagnostic criteria for neuromyelitis optica Neurology 66 1485 1489 2006 16717206
  5. [5]Cabre P MS and neuromyelitis optica in Martinique (French West Indies) Neurology 56 507 514 2001 11222796
  6. [6]Cabrera-Gomez JA Kurtzke JF Gonzalez-Quevedo A Lara-Rodriguez R An epidemiological study of neuromyelitis optica in Cuba J Neurol 256 35 44 2009 19224310
  7. [7]Asgari N A population-based study of neuromyelitis optica in Caucasians Neurology 76 1589 1595 2011 21536639 PMC3269768
  8. [8]Banwell B Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders Neurology 70 344 352 2008 18094334
  9. [9]Nagaishi A Clinical features of neuromyelitis optica in a large Japanese cohort: comparison between phenotypes J Neurol Neurosurg Psychiatry 82 1360 1364 2011 21665917
  10. [10]Jarius S Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients J Neuroinflammation 9 14 2012 22260418 PMC3283476
  11. [11]Jacob A Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders J Neurol Neurosurg Psychiatry 84 922 930 2013 23142960
  12. [12]Papadopoulos MC Verkman AS Aquaporin 4 and neuromyelitis optica Lancet Neurol 11 535 544 2012 22608667 PMC3678971
  13. [13]Iyer A Elsone L Appleton R Jacob A A review of the current literature and a guide to the early diagnosis of autoimmune disorders associated with neuromyelitis optica Autoimmunity 47 154 161 2014 24512514
  14. [14]Matiello M Genetic analysis of aquaporin-4 in neuromyelitis optica Neurology 77 1149 1155 2011 21900637
  15. [15]Matsushita T Association of the HLA-DPB1* 0501 allele with anti-aquaporin-4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders Tissue Antigens 73 171 176 2009 19140826
  16. [16]Brum DG HLA-DRB association in neuromyelitis optica is different from that observed in multiple sclerosis Mult Scler 16 21 29 2010 19995845
  17. [17]Deschamps R Different HLA class II (DRB1 and DQB1) alleles determine either susceptibility or resistance to NMO and multiple sclerosis among the French Afro-Caribbean population Mult Scler 17 24 31 2011 20861181
  18. [18]Zephir H Is neuromyelitis optica associated with human leukocyte antigen? Mult Scler 15 571 579 2009 19299434
  19. [19]Matiello M Familial neuromyelitis optica Neurology 75 310 315 2010 20660861 PMC2918892
  20. [20]Matsuoka T Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese Brain 130 1206 1223 2007 17439988
  21. [21]Nakashima I Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG J Neurol Neurosurg Psychiatry 77 1073 1075 2006 16505005 PMC2077753
  22. [22]Wu JS Zhang MN Carroll WM Kermode AG Characterisation of the spectrum of demyelinating disease in Western Australia J Neurol Neurosurg Psychiatry 79 1022 1026 2008 18356258
  23. [23]Weinshenker BG Wingerchuk DM The two faces of neuromyelitis optica Neurology 82 466 467 2014 24415570
  24. [24]Jarius S Wildemann B AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance Nat Rev Neurol 6 383 392 2010 20639914
  25. [25]Jarius S Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica Nat Clin Pract Neurol 4 202 214 2008 18334978
  26. [27]Koga M Takahashi T Kawai M Fujihara K Kanda T A serological analysis of viral and bacterial infections associated with neuromyelitis optica J Neurol Sci 300 19 22 2011 21056429
  27. [28]Shimizu F Sera from neuromyelitis optica patients disrupt the blood-brain barrier J Neurol Neurosurg Psychiatry 83 288 297 2012 22100760
  28. [29]Jarius S Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance J Neuroinflammation 7 52 2010 20825655 PMC2945323
  29. [30]Kalluri SR Quantification and functional characterization of antibodies to native aquaporin 4 in neuromyelitis optica Arch Neurol 67 1201 1208 2010 20937947
  30. [31]Chihara N Plasmablasts as migratory IgG-producing cells in the pathogenesis of neuromyelitis optica PLoS ONE 8 e83036 2013 24340077 PMC3858367
  31. [32]Bradl M Lassmann DH Anti-aquaporin-4 antibodies in neuromyelitis optica: how to prove their pathogenetic relevance? Int MS J 15 75 78 2008 18812056
  32. [33]Saadoun S Intra-cerebral injection of neuromyelitis optica immunoglobulin G. and human complement produces neuromyelitis optica lesions in mice Brain 133 349 361 2010 20047900 PMC2822632
  33. [34]Bennett JL Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica Ann Neurol 66 617 629 2009 19938104 PMC3180961
  34. [35]Zhang H Bennett JL Verkman AS Ex vivo spinal cord slice model of neuromyelitis optica reveals novel immunopathogenic mechanisms Ann Neurol 70 943 954 2011 22069219 PMC3319401
  35. [36]Ratelade J Neuromyelitis optica IgG and natural killer cells produce NMO lesions in mice without myelin loss Acta Neuropathol 123 861 872 2012 22526022 PMC3581313
  36. [37]Saadoun S Neutrophil protease inhibition reduces neuromyelitis optica-immunoglobulin G-induced damage in mouse brain Ann Neurol 71 323 333 2012 22374891 PMC3643520
  37. [38]Ratelade J Involvement of antibody-dependent cell-mediated cytotoxicity in inflammatory demyelination in a mouse model of neuromyelitis optica Acta Neuropathol 126 699 709 2013 23995423 PMC3890328
  38. [39]Wrzos C Early loss of oligodendrocytes in human and experimental neuromyelitis optica lesions Acta Neuropathol 127 523 538 2014 24292009 PMC4229038
  39. [40]Pohl M T cell-activation in neuromyelitis optica lesions plays a role in their formation Acta Neuropathol Commun 1 85 2013 24367907 PMC3879999
  40. [41]Saadoun S Bridges LR Verkman AS Papadopoulos MC Paucity of natural killer and cytotoxic T cells in human neuromyelitis optica lesions Neuroreport 23 1044 1047 2012 23108041 PMC3590012
  41. [42]Saadoun S T cell deficiency does not reduce lesions in mice produced by intracerebral injection of NMO-IgG and complement J Neuroimmunol 235 27 32 2011 21492943
  42. [43]Hinson SR Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by downregulating EAAT2 J Exp Med 205 2473 2481 2008 18838545 PMC2571922
  43. [44]Hinson SR Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes Proc Natl Acad Sci USA 109 1245 1250 2012 22128336 PMC3268278
  44. [45]Rossi A Ratelade J Papadopoulos MC Bennett JL Verkman AS Neuromyelitis optica IgG does not alter aquaporin-4 water permeability, plasma membrane M1/M23 isoform content, or supramolecular assembly Glia 60 2027 2039 2012 22987455 PMC3586219
  45. [46]Ratelade J Bennett JL Verkman AS Evidence against cellular internalization in vivo of NMO-IgG, aquaporin-4, and excitatory amino acid transporter 2 in neuromyelitis optica J Biol Chem 286 45156 45164 2011 22069320 PMC3247969
  46. [47]Faulkner JR Reactive astrocytes protect tissue and preserve function after spinal cord injury J Neurosci 24 2143 2155 2004 14999065 PMC6730429
  47. [48]Voskuhl RR Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS J Neurosci 29 11511 11522 2009 19759299 PMC2768309
  48. [49]Trebst C Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS) J Neurol 261 1 16 2014 24272588 PMC3895189
  49. [50]Kimbrough DJ Treatment of neuromyelitis optica: review and recommendations Mult Scler Relat Disord 1 180 187 2012 24555176 PMC3926208
  50. [51]Wingerchuk DM Pittock SJ Lucchinetti CF Lennon VA Weinshenker BG A secondary progressive clinical course is uncommon in neuromyelitis optica Neurology 68 603 605 2007 17310032
  51. [52]Barnes PJ Corticosteroids: the drugs to beat Eur J Pharmacol 533 2 14 2006 16436275
  52. [54]Wang HH Interleukin-17-secreting T cells in neuromyelitis optica and multiple sclerosis during relapse J Clin Neurosci 18 1313 1317 2011 21795048
  53. [55]Muls N Upregulation of IL-17, but not of IL-9, in circulating cells of CIS and relapsing MS patients. Impact of corticosteroid therapy on the cytokine network J Neuroimmunol 243 73 80 2012 22245284
  54. [56]Reeves HM Winters JL The mechanisms of action of plasma exchange Br J Haematol 164 342 351 2014 24172059
  55. [57]Bonnan M Cabre P Plasma exchange in severe attacks of neuromyelitis optica Mult Scler Int 2012 787630 2012 22474589 PMC3306943
  56. [58]Bonnan M Plasma exchange in severe spinal attacks associated with neuromyelitis optica spectrum disorder Mult Scler 15 487 492 2009 19324982
  57. [59]Keegan M Plasma exchange for severe attacks of CNS demyelination: predictors of response Neurology 58 143 146 2002 11781423
  58. [60]Merle H Treatment of optic neuritis by plasma exchange (add-on) in neuromyelitis optica Arch Ophthalmol 130 858 862 2012 22776923
  59. [61]Elsone L Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients Mult Scler 20 501 504 2014 23986097
  60. [62]Greenberg BM Idiopathic transverse myelitis: corticosteroids, plasma exchange, or cyclophosphamide Neurology 68 1614 1617 2007 17485649
  61. [63]Kitley J Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan Brain 135 1834 1849 2012 22577216
  62. [64]Watanabe S Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis Mult Scler 13 968 974 2007 17623727
  63. [65]Miyamoto K Kusunoki S Intermittent plasmapheresis prevents recurrence in neuromyelitis optica Ther Apher Dial 13 505 508 2009 19954473
  64. [66]Costanzi C Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica Neurology 77 659 666 2011 21813788
  65. [67]Bichuetti DB Lobato de Oliveira EM Oliveira DM Amorin de Souza N Gabbai AA Neuromyelitis optica treatment: analysis of 36 patients Arch Neurol 67 1131 1136 2010 20837859
  66. [68]Sahraian MA Moinfar Z Khorramnia S Ebrahim MM Relapsing neuromyelitis optica: demographic and clinical features in Iranian patients Eur J Neurol 17 794 799 2010 20100229 J Neurol Neurosurg Psychiatry 82 1360 1364 2011 21665917
  67. [69]Jacob A Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients Arch Neurol 66 1128 1133 2009 19752302
  68. [70]Kitley J Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies J Neurol Neurosurg Psychiatry 84 918 921 2013 23467418
  69. [71]Kim SH Efficacy and safety of mitoxantrone in patients with highly relapsing neuromyelitis optica Arch Neurol 68 473 479 2010 21149806
  70. [72]Yaguchi H Efficacy of intravenous cyclophosphamide therapy for neuromyelitis optica spectrum disorder Intern Med 52 969 972 2013 23648715
  71. [73]Bichuetti DB Oliveira EM de Boulos FC Gabbai AA Lack of response to pulse cyclophosphamide in neuromyelitis optica: evaluation of 7 patients Arch Neurol 69 938 939 2012 22777264
  72. [74]Cree BA An open label study of the effects of rituximab in neuromyelitis optica Neurology 64 1270 1272 2005 15824362
  73. [75]Jacob A Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients Arch Neurol 65 1443 1448 2008 18779415
  74. [76]Kim SH Kim W Li XF Jung IJ Kim HJ Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years Arch Neurol 68 1412 1420 2011 21747007
  75. [77]Bedi GS Impact of rituximab on relapse rate and disability in neuromyelitis optica Mult Scler 17 1225 1230 2011 21622594
  76. [78]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 70 1110 1117 2013 23897062
  77. [79]Greenberg BM Rituximab dosing and monitoring strategies in neuromyelitis optica patients: creating strategies for therapeutic success Mult Scler 18 1022 1026 2012 22261118
  78. [80]Jarius S Antibody to aquaporin-4 in the long-term course of neuromyelitis optica Brain 131 3072 3080 2008 18945724 PMC2577801
  79. [81]Pellkofer HL Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab Neurology 76 1310 1315 2011 21482945
  80. [82]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 70 1110 1117 2013 23897062
  81. [83]Carson KR 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 10 816 824 2009 19647202
  82. [84]Kageyama T Combination of cyclosporine A with corticosteroids is effective for the treatment of neuromyelitis optica J Neurol 260 627 634 2013 23076828
  83. [85]Bourre B Neuromyelitis optica and pregnancy Neurology 78 875 879 2012 22402855
  84. [86]Kim W Influence of pregnancy on neuromyelitis optica spectrum disorder Neurology 78 1264 1267 2012 22491862
  85. [87]Ringelstein M 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 19 1544 1547 2013 23886825
  86. [88]Wen H Ontogeny of water transport in rat brain: postnatal expression of the aquaporin-4 water channel Eur J Neurosci 11 935 945 1999 10103087
  87. [89]Gomori E Fetal development of membrane water channel proteins aquaporin-1 and aquaporin-4 in the human brain Int J Dev Neurosci 24 295 305 2006 16814974
  88. [90]Saadoun S Neuromyelitis optica IgG causes placental inflammation and fetal death J Immunol 191 2999 3005 2013 23935196 PMC4161708
  89. [91]Damiano AE Review: water channel proteins in the human placenta and fetal membranes Placenta 32 Suppl 2 S207 S211 2011 21208655
  90. [92]De Falco M Down-regulation of aquaporin 4 in human placenta throughout pregnancy In Vivo 21 813 817 2007 18019416
  91. [93]Reuss R A woman with acute myelopathy in pregnancy: case outcome BMJ 339 b4026 2009 20007656
  92. [94]Fragoso YD Neuromyelitis optica and pregnancy J Neurol 260 2614 2619 2013 23835638
  93. [95]Pellkofer HL Suessmair C Schulze A Hohlfeld R Kuempfel T Course of neuromyelitis optica during inadvertent pregnancy in a patient treated with rituximab Mult Scler 15 1006 1008 2009 19667025
  94. [96]Yuksel D Senbil N Yilmaz D Yavuz Gurer YK Devic’s neuromyelitis optica in an infant case J Child Neurol 22 1143 1146 2007 17890418
  95. [97]Tillema JM McKeon A The spectrum of neuromyelitis optica (NMO) in childhood J Child Neurol 27 1437 1447 2012 22859697
  96. [98]McKeon A CNS aquaporin-4 autoimmunity in children Neurology 71 93 100 2008 18509092
  97. [99]Lotze TE Spectrum of pediatric neuromyelitis optica Pediatrics 122 e1039 e1047 2008 18838462
  98. [100]Huppke P Neuromyelitis optica and NMO-IgG in European pediatric patients Neurology 75 1740 1804 2010 21060098
  99. [101]Kim SH Kim W Li XF Jung IJ Kim HJ Does interferon beta treatment exacerbate neuromyelitis optica spectrum disorder? Mult Scler 18 1480 1483 2012 22354738
  100. [102]Palace J Leite MI Nairne A Vincent A Interferon beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers Arch Neurol 67 1016 1017 2010 20697055
  101. [103]Shimizu J IFNβ-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis optica spectrum Neurology 75 1423 1427 2010 20826711
  102. [104]Warabi Y Matsumoto Y Hayashi H Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination J Neurol Sci 252 57 61 2007 17125797
  103. [105]Axtell RC Raman C Steinman L Type I interferons: beneficial in Th1 and detrimental in Th17 autoimmunity Clin Rev Allergy Immunol 44 114 120 2012 22231516 PMC5478162
  104. [106]Kleiter I Failure of natalizumab to prevent relapses in neuromyelitis optica Arch Neurol 69 239 245 2012 22332191
  105. [107]Barnett M Prineas J Buckland M Parratt J Pollard J Massive astrocyte destruction in neuromyelitis optica despite natalizumab therapy Mult Scler 18 108 112 2012 21868485
  106. [108]Kitley J Catastrophic brain relapse in seronegative NMO after a single dose of natalizumab J Neurol Sci 339 223 225 2014 24576801
  107. [109]Kleiter I Failure of natalizumab to prevent relapses in neuromyelitis optica Arch Neurol 69 239 245 2012 22332191
  108. [110]Polman CH A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis N Engl J Med 354 899 910 2006 16510744
  109. [111]Lucchinetti CF A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica Brain 125 1450 1461 2002 12076996 PMC5444467
  110. [112]Zhang H Verkman AS Eosinophil pathogenicity mechanisms and therapeutics in neuromyelitis optica J Clin Invest 123 2306 2316 2013 23563310 PMC3635742
  111. [113]Chu VT Eosinophils are required for the maintenance of plasma cells in the bone marrow Nat Immunol 12 151 159 2011 21217761
  112. [114]Min JH Kim BJ Lee KH Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder Mult Scler 18 113 115 2012 22146605
  113. [115]Izaki S A case of neuromyelitis optica spectrum disorder developing a fulminant course with multiple white-matter lesions following fingolimod treatment [Japanese] Rinsho Shinkeigaku 53 513 517 2013 23892961
  114. [116]Sugita K FTY720 regulates bone marrow egress of eosinophils and modulates late-phase skin reaction in mice Am J Pathol 177 1881 1887 2010 20802177 PMC2947283
  115. [117]Pittock SJ Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study Lancet Neurol 12 554 562 2013 23623397
  116. [118]Chihara N Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica Proc Natl Acad Sci USA 108 3701 3706 2011 21321193 PMC3048150
  117. [119]Uzawa A Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks Clin Chim Acta 421 181 183 2013 23535508
  118. [120]Wang H Notable increased cerebrospinal fluid levels of soluble interleukin-6 receptors in neuromyelitis optica Neuroimmunomodulation 19 304 308 2012 22777162
  119. [121]Araki M Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab Mod Rheumatol 23 827 831 2013 22782533 PMC3713263
  120. [122]Ayzenberg I Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy JAMA Neurol 70 394 397 2013 23358868
  121. [123]Kieseier BC Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses JAMA Neurol 70 390 393 2013 23599943
  122. [124]Komai T Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: a case report Mod Rheumatol http://dx.doi.org/10.3109/14397595.2013.861333 24313919 · DOI
  123. [125]Asavapanumas N Ratelade J Verkman AS Unique neuromyelitis optica pathology produced in naive rats by intracerebral administration of NMO-IgG Acta Neuropathol 127 539 551 2014 24190619 PMC3954950
  124. [126]Jarius S Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: results from 211 lumbar punctures J Neurol Sci 306 82 90 2011 21550068
  125. [127]Jacob A Detrimental role of granulocyte-colony stimulating factor in neuromyelitis optica: clinical case and histological evidence Mult Scler 18 1801 1803 2012 22495946
  126. [128]Young RE Neutrophil elastase (NE)-deficient mice demonstrate a nonredundant role for NE in neutrophil migration, generation of proinflammatory mediators, and phagocytosis in response to zymosan particles in vivo J Immunol 172 4493 4502 2004 15034066
  127. [129]Papayannopoulos V Metzler KD Hakkim A Zychlinsky A Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps J Cell Biol 191 677 691 2010 20974816 PMC3003309
  128. [130]Iwata K Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis Intern Med 49 2423 2432 2010 21088343
  129. [132]Kita H Eosinophils: multifaceted biological properties and roles in health and disease Immunol Rev 242 161 177 2011 21682744 PMC3139217
  130. [133]Imbach P High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood Lancet 1 1228 1231 1981 6112565
  131. [134]Gelfand EW Intravenous immune globulin in autoimmune and inflammatory diseases N Engl J Med 367 2015 2025 2012 23171098
  132. [135]Jacob S Rajabally YA Current proposed mechanisms of action of intravenous immunoglobulins in inflammatory neuropathies Curr Neuropharmacol 7 337 342 2009 20514213 PMC2811867
  133. [136]Magraner MJ Coret F Casanova B The effect of intravenous immunoglobulin on neuromyelitis optica Neurologia 28 65 72 2013 22841880
  134. [137]Bakker J Metz L Devic’s neuromyelitis optica treated with intravenous gamma globulin (IVIG) Can J Neurol Sci 31 265 267 2004 15198456
  135. [138]Okada K Tsuji S Tanaka K Intermittent intravenous immunoglobulin successfully prevents relapses of neuromyelitis optica Intern Med 46 1671 1672 2007 17917332
  136. [139]Ratelade J Smith AJ Verkman AS Intravenous immunoglobulin (IVIg) reduces the pathogenicity of aquaporin-4 autoantibodies in neuromyelitis optica Exp Neurol 255 145 153 2014 24636863 PMC4291172
  137. [140]Tedder TF CD19: a promising B cell target for rheumatoid arthritis Nat Rev Rheumatol 5 572 577 2009 19798033
  138. [141]Hammer O CD19 as an attractive target for antibody-based therapy MAbs 4 571 577 2012 22820352 PMC3499297
  139. [142]Kim S Steelman AJ Koito H Li J Astrocytes promote TNF-mediated toxicity to oligodendrocyte precursors J Neurochem 116 53 66 2011 21044081 PMC3057964
  140. [143]Pentón-Rol G TNF-α and IL-10 downregulation and marked oxidative stress in neuromyelitis optica J Inflamm (Lond) 6 18 2009 19490629 PMC2694781
  141. [144]Tradtrantip L Anti-aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica Ann Neurol 71 314 322 2012 22271321 PMC3314396
  142. [145]Tradtrantip L Small-molecule inhibitors of NMO-IgG binding to aquaporin-4 reduce astrocyte cytotoxicity in neuromyelitis optica FASEB J 26 2197 2208 2012 22319008 PMC3336779
  143. [146]Phuan PW A small-molecule screen yields idiotype-specific blockers of neuromyelitis optica immunoglobulin G binding to aquaporin-4 J Biol Chem 287 36837 36844 2012 22989877 PMC3481286
  144. [147]Crane JM Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays J Biol Chem 286 16516 16524 2011 21454592 PMC3091256
  145. [148]Phuan PW Ratelade J Rossi A Tradtrantip L Verkman AS Complement-dependent cytotoxicity in neuromyelitis optica requires aquaporin-4 protein assembly in orthogonal arrays J Biol Chem 287 13829 13839 2012 22393049 PMC3340190
  146. [149]Jarius S Wildemann B Aquaporin-4 antibodies, CNS acidosis and neuromyelitis optica: a potential link Med Hypotheses 81 1090 1095 2013 24182872
  147. [150]Warth A Prevention of orthogonal array of particles formation as a treatment approach for neuromyelitis optica Med Hypotheses 73 361 362 2009 19398170
  148. [151]Collin M Olsen A EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG EMBO J 20 3046 3055 2001 11406581 PMC150189
  149. [152]Tradtrantip L Ratelade J Zhang H Verkman AS Enzymatic deglycosylation converts pathogenic neuromyelitis optica anti-aquaporin-4 immunoglobulin G. into therapeutic antibody Ann Neurol 73 77 85 2013 23055279 PMC3567850
  150. [153]Tradtrantip L Asavapanumas N Verkman AS Therapeutic cleavage of anti-aquaporin-4 autoantibody in neuromyelitis optica by an IgG-selective proteinase Mol Pharmacol 83 1268 1275 2013 23571414 PMC3657102
  151. [154]Lewis LA Ram S Meningococcal disease and the complement system Virulence 5 98 126 2014 24104403 PMC3916388
  152. [155]Phuan PW C1q-targeted monoclonal antibody prevents complement-dependent cytotoxicity and neuropathology in in vitro and mouse models of neuromyelitis optica Acta Neuropathol 125 829 840 2013 23677375 PMC3941651
  153. [156]Ricklin D Lambris JD Complement-targeted therapeutics Nat Biotechnol 25 1265 1275 2007 17989689 PMC2966895
  154. [157]Ricklin D Lambris JD Progress and trends in complement therapeutics Adv Exp Med Biol 735 1 22 2013 PMC3526805 22990692
  155. [158]Davies A Lachmann PJ Membrane defence against complement lysis: the structure and biological properties of CD59 Immunol Res 12 258 275 1993 7507156
  156. [159]Zipfel PF Skerka C Complement regulators and inhibitory proteins Nat Rev Immunol 9 729 740 2009 19730437
  157. [160]Botto M Complement in human diseases: lessons from complement deficiencies Mol Immunol 46 2774 2783 2009 19481265
  158. [161]Asavapanumas N Experimental mouse model of optic neuritis with inflammatory demyelination produced by passive transfer of neuromyelitis optica-immunoglobulin G J Neuroinflammation 11 16 2014 24468108 PMC3909205
  159. [162]Zhang H Verkman AS Longitudinally extensive NMO spinal cord pathology produced by passive transfer of NMO-IgG in mice lacking complement inhibitor CD59 J Autoimmun http://dx.doi.org/10.1016/j.jaut.2014.02.011 PMC4162764 24698947 · DOI
  160. [163]Vincent T Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood–brain barrier permeability and granulocyte recruitment J Immunol 181 5730 5737 2008 18832732
  161. [164]Mihai S Nimmerjahn F The role of Fc receptors and complement in autoimmunity Autoimmun Rev 12 657 660 2013 23201918
  162. [165]Hosokawa T Increased serum matrix metalloproteinase-9 in neuromyelitis optica: implication of disruption of blood-brain barrier J Neuroimmunol 236 81 86 2011 21621856
  163. [166]Bluestone JA Bour-Jordan H Current and future immunomodulation strategies to restore tolerance in autoimmune diseases Cold Spring Harb Perspect Biol 4 2012 PMC3536337 23125012
  164. [167]Bar-Or A Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial Arch Neurol 64 1407 1415 2007 17698695
  165. [168]Faria AMC Weiner HL Oral tolerance: therapeutic implications for autoimmune diseases Clin Dev Immunol 13 143 157 2006 17162357 PMC2270752
  166. [169]Bielekova B Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand Nat Med 6 1167 1175 2000 11017150
  167. [170]Fagius J Lundgren J Oberg G Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation Mult Scler 15 229 237 2008 18805841
  168. [171]Illei GG Current state and future directions of autologous hematopoietic stem cell transplantation in systemic lupus erythematosus Ann Rheum Dis 70 2071 2074 2011 21873334 PMC3923531
  169. [172]Mader S Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders J Neuroinflammation 8 184 2011 22204662 PMC3278385
  170. [173]Kitley J Longitudinally extensive transverse myelitis with and without aquaporin 4 antibodies JAMA Neurol 70 1375 1381 2013 23999580
  171. [174]Kitley J Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study JAMA Neurol 71 276 283 2014 24425068
  172. [175]Kitley J Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype Neurology 79 1273 1277 2012 22914827
  173. [176]Rostasy K Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica Mult Scler 19 1052 1059 2013 23257621
  174. [178]Reindl M Di Pauli F Rostasy K Berger T The spectrum of MOG autoantibody-associated demyelinating diseases Nat Rev Neurol 9 455 461 2013 23797245
  175. [179]Saadoun S Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain Acta Neuropathol Commun 2 35 2014 24685353 PMC3977893
  176. [180]Mealy MA Wingerchuk DM Palace J Greenberg BM Levy M Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy JAMA Neurol 71 324 330 2014 24445513
  177. [181]Pellkofer HL Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab Neurology 76 1310 1315 2011 21482945
  178. [182]Weinstock-Guttman B Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease) Arch Neurol 63 957 963 2006 16831964
  179. [183]Li Y Wang H Long Y Lu Z Hu X Increased memory Th17 cells in patients with neuromyelitis optica and multiple sclerosis J Neuroimmunol 234 155 160 2011 21489641
  180. [184]Raveendra BL Discovery of peptoid ligands for anti-aquaporin 4 antibodies Chem Biol 20 351 359 2013 23521793 PMC3640264

Cited by

Sorted by citations

Authors
Papadopoulos, M. C., Bennett, J. L., & Verkman, A. S.
Affiliations
  • St George's, University of London (GB)
  • University of Colorado Anschutz (US)
  • University of California, San Francisco (US)
Corresponding author
Papadopoulos, Marios C.
ORCID
Venue
Nature Reviews Neurology
Publisher
Springer Science and Business Media LLC
Published
2014-08-12
Volume
10
Issue
9
Pages
493-506
ISSN
  • 1759-4758 (ISSN-L)
  • 1759-4766
DOI
10.1038/nrneurol.2014.141
PMC
PMC4229040
OpenAlex
W2069414099
Cited by
262
References
4
Citations by year
2026: 6 · 2025: 20 · 2024: 14 · 2023: 17 · 2022: 25 · 2021: 26 · 2020: 24 · 2019: 31 · 2018: 16 · 2017: 33 · 2016: 29 · 2015: 20 · 2014: 1
FWCI
3.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Neurology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Guthy-Jackson Charitable Foundation
  • National Institutes of Health
  • National Eye Institute (R01EY013574, R01EY022936)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK035124)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Keywords
neuromyelitis optica, aquaporin-4, complement-dependent cytotoxicity, demyelination, immunosuppressive therapy, B-cell depletion, plasma exchange, drug repurposing, IL-6 receptor, neutrophils, eosinophils, CD19, blood-brain barrier, immune tolerance, multiple sclerosis differential diagnosis
MeSH terms
Humans, Neuromyelitis Optica

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