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  • Review Article
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AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance

Nature Reviews Neurology volume 6, pages 383–392 (2010)Cite this article

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Abstract

Antibodies to aquaporin-4 (also known as AQP4-Ab or NMO-IgG) are sensitive and highly specific serum markers of autoimmune neuromyelitis optica (NMO). Second-generation recombinant diagnostic assays can detect AQP4-Ab in ≥80% of patients with NMO, and a role for AQP4-Ab in the pathophysiology of this condition was corroborated by a series of in vitro studies that demonstrated disruption of the blood–brain barrier, impairment of glutamate homeostasis and induction of necrotic cell death by AQP4-Ab-positive serum. Additional evidence for such a role has emerged from clinical observations, including the demonstration of a correlation between serum levels of AQP4-Ab and disease activity. The finding of NMO-like CNS lesions and clinical disease following passive transfer of AQP4-Ab-positive serum in several independent animal studies provided definitive proof for a pathogenic role of AQP4-Ab in vivo. Together, these findings provide a strong rationale for the use of therapies targeted against B cells or antibodies in the treatment of NMO. In this Review, we summarize the latest evidence in support of a direct involvement of AQP4-Ab in the immunopathogenesis of NMO, and critically appraise the diagnostic tests currently available for the detection of this serum reactivity.

Key Points

  • Growing evidence implicates aquaporin-4 antibody (AQP4-Ab)-mediated autoimmunity in the pathogenesis of neuromyelitis optica (NMO) and its formes frustes, but not in multiple sclerosis or other CNS autoimmune conditions

  • Robust evidence for a direct involvement of AQP4-Ab in NMO immunopathogenesis comes from animal studies reporting NMO-like disease after passive transfer of AQP4-Ab-positive human serum

  • A strong rationale exists for the use of therapies targeting B cells or antibodies in NMO, and this will be an important consideration for future treatment trials

  • Second-generation recombinant serological assays with higher sensitivity and specificity than the original 'NMO-IgG' test are now available and should be offered to all patients with NMO or related disorders

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Figure 1: Histopathological findings in NMO, MS and EAE.
Figure 2: Ribbon diagrams of a human AQP4 homotetramer.
Figure 3: Freeze fracture images showing the plasma membrane of CHO cells.
Figure 4: Detection of AQP4-Ab by indirect immunofluorescence techniques.

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References

  1. Wingerchuk, D. M., Hogancamp, W. F., O'Brien, P. C. & Weinshenker, B. G. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology 53, 1107–1114 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. de Seze, J. et al. Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile. J. Neurol. Sci. 197, 57–61 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Jarius, S. et al. Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica. Nat. Clin. Pract. Neurol. 4, 202–214 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. Lucchinetti, C. F. et al. A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain 125, 1450–1461 (2002).

    Article  PubMed  Google Scholar 

  5. Weinshenker, B. G. et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann. Neurol. 46, 878–886 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Keegan, M. et al. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 58, 143–146 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Lennon, V. A. et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364, 2106–2112 (2004).

    Article  CAS  PubMed  Google Scholar 

  8. Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S. & Hinson, S. R. IgG marker of optic–spinal multiple sclerosis binds to the aquaporin-4 water channel. J. Exp. Med. 202, 473–477 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Roemer, S. F. et al. Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain 130, 1194–1205 (2007).

    Article  PubMed  Google Scholar 

  10. Misu, T. et al. Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis. Brain 130, 1224–1234 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Weinshenker, B. G. et al. Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann. Neurol. 59, 566–569 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Matiello, M. et al. NMO-IgG predicts the outcome of recurrent optic neuritis. Neurology 70, 2197–2200 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. Takahashi, T. et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 130, 1235–1243 (2007).

    Article  PubMed  Google Scholar 

  14. Jarius, S. et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 131, 3072–3080 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bonnan, M. et al. Plasma exchange in severe spinal attacks associated with neuromyelitis optica spectrum disorder. Mult. Scler. 15, 487–492 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Watanabe, S. et al. Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica. Mult. Scler. 13, 128–132 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Nakashima, I. et al. Plasma exchange for neuromyelitis optica with aquaporin-4 antibody [abstract P04.092]. Neurology 72 (Suppl. 3), A187 (2009).

    Google Scholar 

  18. Cree, B. A. et al. An open label study of the effects of rituximab in neuromyelitis optica. Neurology 64, 1270–1272 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Jacob, A. et al. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch. Neurol. 65, 1443–1448 (2008).

    Article  PubMed  Google Scholar 

  20. Bedi, G. S., Brown, A., Delgado, S., Usmani, N. & Sheremata, W. Effect of rituximab on relapse rate and disability in neuromyelitis optica (NMO) [abstract P04.099]. Neurology 72 (Suppl. 3), A189 (2009).

    Google Scholar 

  21. Heerlein, K. et al. Aquaporin-4 antibody positive longitudinally extensive transverse myelitis following varicella zoster infection. J. Neurol. Sci. 276, 184–186 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Suzuki, C. et al. Anti-aquaporin-4 antibody production from peripheral B cells in neuromyelitis optica [abstract S39.005]. Neurology 72 (Suppl. 3), A281 (2009).

    Google Scholar 

  23. Meinl, E., Krumbholz, M. & Hohlfeld, R. B lineage cells in the inflammatory central nervous system environment: migration, maintenance, local antibody production, and therapeutic modulation. Ann. Neurol. 59, 880–892 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Sinclair, C., Kirk, J., Herron, B., Fitzgerald, U. & McQuaid, S. Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter. Acta Neuropathol. (Berl.) 113, 187–194 (2007).

    Article  CAS  Google Scholar 

  25. Misu, T. et al. Loss of aquaporin-4 in active perivascular lesions in neuromyelitis optica: a case report. Tohoku J. Exp. Med. 209, 269–275 (2006).

    Article  PubMed  Google Scholar 

  26. Saadoun, S. et al. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain 133, 349–361 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yanagawa, K. et al. Pathologic and immunologic profiles of a limited form of neuromyelitis optica with myelitis. Neurology 73, 1628–1637 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Kale, N. et al. Humoral pattern II multiple sclerosis pathology not associated with neuromyelitis optica IgG. Arch. Neurol. 66, 1298–1299 (2009).

    Article  PubMed  Google Scholar 

  29. Misu, T. et al. Marked increase in cerebrospinal fluid glial fibrillar acidic protein in neuromyelitis optica: an astrocytic damage marker. J. Neurol. Neurosurg. Psychiatry 80, 575–577 (2009).

    Article  CAS  PubMed  Google Scholar 

  30. Miyazawa, I. et al. High CSF neurofilament heavy chain levels in neuromyelitis optica. Neurology 68, 865–867 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Uzawa, A. et al. Markedly increased CSF interleukin-6 levels in neuromyelitis optica, but not in multiple sclerosis. J. Neurol. 256, 2082–2084 (2009).

    Article  CAS  PubMed  Google Scholar 

  32. Okada, K., Matsushita, T., Kira, J. & Tsuji, S. B-cell activating factor of the TNF family is upregulated in neuromyelitis optica. Neurology 74, 177–178 (2010).

    Article  PubMed  Google Scholar 

  33. Icoz, S. et al. Enhanced IL-6 production in aquaporin-4 antibody positive neuromyelitis optica patients. Int. J. Neurosci. 120, 71–75 (2010).

    Article  PubMed  Google Scholar 

  34. Alves-Leon, S. V. et al. Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica. Arq. Neuropsiquiatr. 66, 678–684 (2008).

    Article  PubMed  Google Scholar 

  35. Matsushita, T. et al. Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese. Mult. Scler. 15, 834–847 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Correale, J. & Fiol, M. Activation of humoral immunity and eosinophils in neuromyelitis optica. Neurology 63, 2363–2370 (2004).

    Article  PubMed  Google Scholar 

  37. Hinson, S. R. et al. Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 69, 2221–2231 (2007).

    Article  CAS  PubMed  Google Scholar 

  38. Vincent, T. et al. Functional consequences of neuromyelitis optica-IgG astrocyte interactions on blood–brain barrier permeability and granulocyte recruitment. J. Immunol. 181, 5730–5737 (2008).

    Article  CAS  PubMed  Google Scholar 

  39. Hinson, S. R. et al. Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J. Exp. Med. 205, 2473–2481 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kinoshita, M. et al. Anti-aquaporin-4 antibody induces astrocytic cytotoxicity in the absence of CNS antigen-specific T cells. Biochem. Biophys. Res. Commun. 394, 205–210 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Zhou, J. et al. Altered blood–brain barrier integrity in adult aquaporin-4 knockout mice. Neuroreport 19, 1–5 (2008).

    Article  PubMed  Google Scholar 

  42. Matsushita, T. et al. Extensive vasogenic edema of anti-aquaporin-4 antibody-related brain lesions. Mult. Scler. 15, 1113–1117 (2009).

    Article  CAS  PubMed  Google Scholar 

  43. Zeng, X. N. et al. Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes. Mol. Cell. Neurosci. 34, 34–39 (2007).

    Article  CAS  PubMed  Google Scholar 

  44. Matute, C. et al. The link between excitotoxic oligodendroglial death and demyelinating diseases. Trends Neurosci. 24, 224–230 (2001).

    Article  CAS  PubMed  Google Scholar 

  45. Alberdi, E. et al. Activation of kainate receptors sensitizes oligodendrocytes to complement attack. J. Neurosci. 26, 3220–3228 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Waters, P. et al. Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch. Neurol. 65, 913–919 (2008).

    Article  PubMed  Google Scholar 

  47. Kalluri, S. R. et al. A novel bio-assay to determine and characterize the antibodies to aquaporin-4 [abstract P04.102]. Neurology 72 (Suppl. 3), A189 (2009).

    Google Scholar 

  48. Matsushita, T. et al. Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese. Mult. Scler. 15, 834–847 (2009).

    Article  CAS  PubMed  Google Scholar 

  49. Spiller, O. B., Moretto, G., Kim, S. U., Morgan, B. P. & Devine, D. V. Complement expression on astrocytes and astrocytoma cell lines: failure of complement regulation at the C3 level correlates with very low CD55 expression. J. Neuroimmunol. 71, 97–106 (1996).

    Article  CAS  PubMed  Google Scholar 

  50. Kinoshita, M. et al. Astrocytic necrosis is induced by anti-aquaporin-4 antibody-positive serum. Neuroreport 20, 508–512 (2009).

    Article  CAS  PubMed  Google Scholar 

  51. Sabater, L. et al. Cytotoxic effect of neuromyelitis optica antibody (NMO-IgG) to astrocytes: an in vitro study. J. Neuroimmunol. 215, 31–35 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Hinson, S. R. et al. Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells. Arch. Neurol. 66, 1164–1167 (2009).

    Article  PubMed  Google Scholar 

  53. Doi, H. et al. Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody. Mult. Scler. 15, 304–310 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Jarius, S., Franciotta, D., Bergamaschi, R., Wildemann, B. & Wandinger, K. P. Immunoglobulin M antibodies to aquaporin-4 in neuromyelitis optica and related disorders. Clin. Chem. Lab. Med. doi: 10.1515/CCLM.2010.127.

  55. Saikali, P., Cayrol, R. & Vincent, T. Anti-aquaporin-4 auto-antibodies orchestrate the pathogenesis in neuromyelitis optica. Autoimmun. Rev. 9, 132–135 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. Tani, T. et al. Identification of binding sites for anti-aquaporin 4 antibodies in patients with neuromyelitis optica. J. Neuroimmunol. 211, 110–113 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Nicchia, G. P. et al. Aquaporin-4 orthogonal arrays of particles are the target for neuromyelitis optica autoantibodies. Glia 57, 1363–1373 (2009).

    Article  PubMed  Google Scholar 

  58. Furman, C. S. et al. Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms. Proc. Natl Acad. Sci. USA 100, 13609–13614 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Matiello, M. et al. Two different Arg19 mutations in the N-terminus of aquaporin-4 suggest a molecular mechanism for susceptibility to neuromyelitis optica [abstract S17.001]. Neurology 72 (Suppl. 3), A119 (2009).

    Google Scholar 

  60. Crane, J. M., Bennett, J. L. & Verkman, A. S. Live cell analysis of aquaporin-4 M1/M23 interactions and regulated orthogonal array assembly in glial cells. J. Biol. Chem. 284, 35850–35860 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Jarius, S. et al. Standardized method for the detection of antibodies to aquaporin-4 based on a highly sensitive immunofluorescence assay employing recombinant target antigen. J. Neurol. Sci. 291, 52–56 (2010).

    Article  CAS  PubMed  Google Scholar 

  62. Paul, F. et al. Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica. PLoS Med. 4, e133 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Marnetto, F. et al. Western blot analysis for the detection of serum antibodies recognizing linear aquaporin-4 epitopes in patients with neuromyelitis optica. J. Neuroimmunol. 217, 74–79 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Kinoshita, M. et al. Neuromyelitis optica: passive transfer to rats by human immunoglobulin. Biochem. Biophys. Res. Commun. 386, 623–627 (2009).

    Article  CAS  PubMed  Google Scholar 

  65. Bradl, M. et al. Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo. Ann. Neurol. 66, 630–643 (2009).

    Article  CAS  PubMed  Google Scholar 

  66. Bennett, J. L. et al. Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann. Neurol. 66, 617–629 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nishiyama, S. et al. A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset. Neurology 72, 1960–1961 (2009).

    Article  CAS  PubMed  Google Scholar 

  68. Jarius, S. et al. Neuromyelitis optica and longitudinally extensive transverse myelitis following thymectomy for myasthenia gravis [abstract P534]. Mult. Scler. 13 (Suppl. 2), S159 (2007).

    Google Scholar 

  69. Ahasan, H. A., Rafiqueuddin, A. K., Chowdhury, M. A., Azhar, M. A. & Kabir, F. Neuromyelitis optica (Devic's disease) following chicken pox. Trop. Doct. 24, 75–76 (1994).

    Article  CAS  PubMed  Google Scholar 

  70. Chusid, M. J., Williamson, S. J., Murphy, J. V. & Ramey, L. S. Neuromyelitis optica (Devic disease) following varicella infection. J. Pediatr. 95, 737–738 (1979).

    Article  CAS  PubMed  Google Scholar 

  71. Tran, C. et al. Neuromyelitis optica following CMV primo-infection. J. Intern. Med. 261, 500–503 (2007).

    Article  CAS  PubMed  Google Scholar 

  72. Ghezzi, A. et al. Clinical characteristics, course and prognosis of relapsing Devic's neuromyelitis optica. J. Neurol. 251, 47–52 (2004).

    Article  PubMed  Google Scholar 

  73. Jarius, S. et al. NMO-IgG in the diagnosis of neuromyelitis optica. Neurology 68, 1076–1077 (2007).

    Article  CAS  PubMed  Google Scholar 

  74. Weinshenker, B. G., Wingerchuk, D. M., Nakashima, I., Fujihara, K. & Lennon, V. A. OSMS is NMO, but not MS: proven clinically and pathologically. Lancet Neurol. 5, 110–111 (2006).

    Article  PubMed  Google Scholar 

  75. Matsuoka, T. et al. Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese. Brain 130, 1206–1223 (2007).

    Article  PubMed  Google Scholar 

  76. Takahashi, T. et al. Establishment of a new sensitive assay for anti-human aquaporin-4 antibody in neuromyelitis optica. Tohoku J. Exp. Med. 210, 307–313 (2006).

    Article  CAS  PubMed  Google Scholar 

  77. Nakashima, I. et al. Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG. J. Neurol. Neurosurg. Psychiatry 77, 1073–1075 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Petzold, A. et al. Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis. J. Neurol. Neurosurg. Psychiatry 81, 109–111 (2010).

    Article  CAS  PubMed  Google Scholar 

  79. Takahashi, T. et al. Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations. J. Neurol. Neurosurg. Psychiatry 79, 1075–1078 (2008).

    Article  CAS  PubMed  Google Scholar 

  80. Pittock, S. J. et al. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch. Neurol. 63, 964–968 (2006).

    Article  PubMed  Google Scholar 

  81. Magana, S. M. et al. Posterior reversible encephalopathy syndrome in neuromyelitis optica spectrum disorders. Neurology 72, 712–717 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Ito, S. Posterior reversible encephalopathy syndrome in neuromyelitis optica spectrum disorders. Neurology 73, 1604 (2009).

    Article  PubMed  Google Scholar 

  83. McKeon, A. et al. CNS aquaporin-4 autoimmunity in children. Neurology 71, 93–100 (2008).

    Article  CAS  PubMed  Google Scholar 

  84. Wandinger, K. P. et al. Autoantibodies against aquaporin-4 in patients with neuropsychiatric SLE and primary Sjögren´s syndrome. Arthritis Rheum. 62, 1198–1200 (2010).

    Article  CAS  PubMed  Google Scholar 

  85. Pittock, S. J. et al. Neuromyelitis optica and non organ-specific autoimmunity. Arch. Neurol. 65, 78–83 (2008).

    PubMed  Google Scholar 

  86. Hayakawa, S. et al. Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay. J. Neuroimmunol. 196, 181–187 (2008).

    Article  CAS  PubMed  Google Scholar 

  87. Pittock, S. J. & Lennon, V. A. Aquaporin-4 autoantibodies in a paraneoplastic context. Arch. Neurol. 65, 629–632 (2008).

    PubMed  Google Scholar 

  88. Cross, S. A. et al. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann. Neurol. 54, 38–50 (2003).

    Article  PubMed  Google Scholar 

  89. Ducray, F. et al. Devic's syndrome-like phenotype associated with thymoma and anti-CV2/CRMP5 antibodies. J. Neurol. Neurosurg. Psychiatry 78, 325–327 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Klawiter, E. C. et al. NMO-IgG detected in CSF in seronegative neuromyelitis optica. Neurology 72, 1101–1103 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cree, B. A., Goodin, D. S. & Hauser, S. L. Neuromyelitis optica. Semin. Neurol. 22, 105–122 (2002).

    Article  PubMed  Google Scholar 

  92. Ho, J. D. et al. Crystal structure of human aquaporin 4 at 1.8 Å and its mechanism of conductance. Proc. Natl Acad. Sci. USA 106, 7437–7442 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Moreland, J. L., Gramada, A., Buzko, O. V., Zhang, Q. & Bourne, P. E. The Molecular Biology Toolkit (MBT): a modular platform for developing molecular visualization applications. BMC Bioinformatics 6, 21 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Adoni, T., Lino, A. M., Marchiori, P. E., Kok, F. & Callegaro, D. Seroprevalence of NMO-IgG antibody in Brazilian patients with neuromyelitis optica. Arq. Neuropsiquiatr. 66, 295–297 (2008).

    Article  PubMed  Google Scholar 

  95. Marignier, R. et al. NMO-IgG and Devic's neuromyelitis optica: a French experience. Mult. Scler. 14, 440–445 (2008).

    Article  PubMed  Google Scholar 

  96. Saiz, A. et al. Revised diagnostic criteria for neuromyelitis optica (NMO): application in a series of suspected patients. J. Neurol. 254, 1233–1237 (2007).

    Article  PubMed  Google Scholar 

  97. Bizzoco, E. et al. Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution. J. Neurol. 256, 1891–1898 (2009).

    Article  PubMed  Google Scholar 

  98. Wingerchuk, D. M., Lennon, V. A., Pittock, S. J., Lucchinetti, C. F. & Weinshenker, B. G. Revised diagnostic criteria for neuromyelitis optica. Neurology 66, 1485–1489 (2006).

    Article  CAS  PubMed  Google Scholar 

  99. Apiwattanakul, M. et al. AQP4-IgG immunoprecipitation assay optimization. Clin. Chem. 55, 592–594 (2009).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The work of S. Jarius was supported by a Research Fellowship from the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS).

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  1. Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Sven Jarius & Brigitte Wildemann

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Correspondence to Brigitte Wildemann.

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The authors have received research grants from Bayer Schering Pharma and Merck Serono. The funding sources had no role in data collection, analysis of data, preparation of the manuscript, or decision to publish this Review.

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Jarius, S., Wildemann, B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 6, 383–392 (2010). https://doi.org/10.1038/nrneurol.2010.72

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