Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Seminars in Immunopathology
Published in: Seminars in Immunopathology 5/2022

30-05-2022 | Multiple Sclerosis | Review

Immuno-pathogenesis of neuromyelitis optica and emerging therapies

Authors: Norio Chihara, Takashi Yamamura

Published in: Seminars in Immunopathology | Issue 5/2022

Login to get access

Abstract

Neuromyelitis optica (NMO) is an inflammatory disease that resembles MS in the relapsing clinical course of optic neuritis and myelitis. Two decades of studies have revealed that autoantibodies, reactive to the water channel protein aquaporin 4 (AQP4) are detected in the core group of patients. These autoantibodies play a crucial role in the inflammatory pathology of NMO, involving proinflammatory cytokines, chemokines, and various inflammatory cells such as Th17 cells. Anti-AQP4 antibody–positive NMO differs fundamentally from MS, particularly in the responsiveness to therapies and the neuropathology accompanying destruction of astrocytes. Research into the immunological mechanism has led to the identification of possible targets of therapy, including complement pathway and interleukin-6 (IL-6) receptor signaling. Recent randomized controlled clinical trials have shown the remarkable efficacy of antibodies specific for complement C5, IL-6 receptor, and CD19+ B cells in prevention of NMO spectrum disorder relapses, although no such effects were found in anti-AQP4 antibody–negative patients. These results imply that anti-AQP4 antibody is a biomarker predicting the efficacy of therapies, and indicate the future direction towards “precision medicine.”
Literature
1.
Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112PubMedCrossRef
2.
Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202:473–477PubMedPubMedCentralCrossRef
3.
Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG (2006) Revised diagnostic criteria for neuromyelitis optica. 2006. Neurology 66:1485–1489PubMedCrossRef
4.
Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K, Greenberg B, Jacob A, Jarius S, Lana-Peixoto M, Levy M, Simon JH, Tenembaum S, Traboulsee AL, Waters P, Wellik KE, Weinshenker BG, International Panel for NMOD (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–89PubMedPubMedCentralCrossRef
5.
Reindl M, Di Pauli F, Rostasy K, Berger T (2013) The spectrum of MOG autoantibody-associated demyelinating diseases. Nat Rev Neurol 9:455–461PubMedCrossRef
6.
Warabi Y, Matsumoto Y, Hayashi H (2007) Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination. J Neurol Sci 252:57–61PubMedCrossRef
7.
Izaki S, Narukawa S, Kubota A, Mitsui T, Fukaura H, Nomura K (2013) A case of neuromyelitis optica spectrum disorder developing a fulminant course with multiple white-matter lesions following fingolimod treatment. Rinsho Shinkeigaku 53:513–517PubMedCrossRef
8.
Jacob A, Hutchinson M, Elsone L, Kelly S, Ali R, Saukans I, Tubridy N, Boggild M (2012) Does natalizumab therapy worsen neuromyelitis optica? Neurology 79:1065–1066PubMedCrossRef
9.
Pittock SJ, Berthele A, Fujihara K, Kim HJ, Levy M, Palace J, Nakashima I, Terzi M, Totolyan N, Viswanathan S, Wang KC, Pace A, Fujita KP, Armstrong R, Wingerchuk DM (2019) Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med 381:614–625PubMedCrossRef
10.
Yamamura T, Kleiter I, Fujihara K, Palace J, Greenberg B, Zakrzewska-Pniewska B, Patti F, Tsai CP, Saiz A, Yamazaki H, Kawata Y, Wright P, De Seze J (2019) Trial of satralizumab in neuromyelitis optica spectrum disorder. N Engl J Med 381:2114–2124PubMedCrossRef
11.
Traboulsee A, Greenberg BM, Bennett JL, Szczechowski L, Fox E, Shkrobot S, Yamamura T, Terada Y, Kawata Y, Wright P, Gianella-Borradori A, Garren H, Weinshenker BG (2020) Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol 19:402–412PubMedPubMedCentralCrossRef
12.
Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, Lublin FD, Drappa J, Barron G, Madani S, Ratchford JN, She D, Cimbora D, Katz E, N-MOmentum study inverstigators (2019) Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 394:1352–1363PubMedCrossRef
13.
Tahara M, Oeda T, Okada K, Kiriyama T, Ochi K, Maruyama H, Fukaura H, Nomura K, Shimizu Y, Mori M, Nakashima I, Misu T, Umemura A, Yamamoto K, Sawada H (2020) Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 19:298–306PubMedCrossRef
14.
Cossburn M, Tackley G, Baker K, Ingram G, Burtonwood M, Malik G, Pickersgill T, te Water Naude J, Robertson N (2012) The prevalence of neuromyelitis optica in South East Wales. Eur J Neurol 19:655–9PubMedCrossRef
15.
Asgari N, Lillevang ST, Skejoe HP, Falah M, Stenager E, Kyvik KO (2011) A population-based study of neuromyelitis optica in Caucasians. Neurology 76:1589–1595PubMedPubMedCentralCrossRef
16.
Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG (2007) The spectrum of neuromyelitis optica. Lancet Neurol 6:805–815PubMedCrossRef
17.
Matiello M, Kim HJ, Kim W, Brum DG, Barreira AA, Kingsbury DJ, Plant GT, Adoni T, Weinshenker BG (2010) Familial neuromyelitis optica. Neurology 75:310–315PubMedPubMedCentralCrossRef
18.
Yoshimura S, Isobe N, Matsushita T, Yonekawa T, Masaki K, Sato S, Kawano Y, Kira J, South Japan Multiple Sclerosis Genetics C (2013) Distinct genetic and infectious profiles in Japanese neuromyelitis optica patients according to anti-aquaporin 4 antibody status. J Neurol Neurosurg Psychiatry 84:29–34PubMedCrossRef
19.
Pittock SJ, Lennon VA, de Seze J, Vermersch P, Homburger HA, Wingerchuk DM, Lucchinetti CF, Zephir H, Moder K, Weinshenker BG (2008) Neuromyelitis optica and non organ-specific autoimmunity. Arch Neurol 65:78–83PubMedCrossRef
20.
Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG (1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 53:1107–1114PubMedCrossRef
21.
Ghezzi A, Bergamaschi R, Martinelli V, Trojano M, Tola MR, Merelli E, Mancardi L, Gallo P, Filippi M, Zaffaroni M, Comi G, Italian Devic’s Study G (2004) Clinical characteristics, course and prognosis of relapsing Devic’s neuromyelitis Optica. J Neurol 251:47–52PubMedCrossRef
22.
Sellner J, Hemmer B, Muhlau M (2010) The clinical spectrum and immunobiology of parainfectious neuromyelitis optica (Devic) syndromes. J Autoimmun 34:371–379PubMedCrossRef
23.
Amiry-Moghaddam M, Ottersen OP (2003) The molecular basis of water transport in the brain. Nat Rev Neurosci 4:991–1001PubMedCrossRef
24.
Kremer L, Mealy M, Jacob A, Nakashima I, Cabre P, Bigi S, Paul F, Jarius S, Aktas O, Elsone L, Mutch K, Levy M, Takai Y, Collongues N, Banwell B, Fujihara K, de Seze J (2014) Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients. Mult Scler 20:843–847PubMedCrossRef
25.
Kanbayashi T, Shimohata T, Nakashima I, Yaguchi H, Yabe I, Nishizawa M, Shimizu T, Nishino S (2009) Symptomatic narcolepsy in patients with neuromyelitis optica and multiple sclerosis: new neurochemical and immunological implications. Arch Neurol 66:1563–1566PubMedCrossRef
26.
27.
Shosha E, Dubey D, Palace J, Nakashima I, Jacob A, Fujihara K, Takahashi T, Whittam D, Leite MI, Misu T, Yoshiki T, Messina S, Elsone L, Majed M, Flanagan E, Gadoth A, Huebert C, Sagen J, Greenberg BM, Levy M, Banerjee A, Weinshenker B, Pittock SJ (2018) Area postrema syndrome: frequency, criteria, and severity in AQP4-IgG-positive NMOSD. Neurology 91:e1642–e1651PubMedPubMedCentralCrossRef
28.
Wang KY, Chetta J, Bains P, Balzer A, Lincoln J, Uribe T, Lincoln CM (2018) Spectrum of MRI brain lesion patterns in neuromyelitis optica spectrum disorder: a pictorial review. Br J Radiol 91:20170690PubMedPubMedCentralCrossRef
29.
Waters PJ, McKeon A, Leite MI, Rajasekharan S, Lennon VA, Villalobos A, Palace J, Mandrekar JN, Vincent A, Bar-Or A, Pittock SJ (2012) Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology 78:665–71PubMedPubMedCentralCrossRef
30.
Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura M, Watanabe S, Shiga Y, Kanaoka C, Fujimori J, Sato S, Itoyama Y (2007) Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 130:1235–1243PubMedCrossRef
31.
Jarius S, Aboul-Enein F, Waters P, Kuenz B, Hauser A, Berger T, Lang W, Reindl M, Vincent A, Kristoferitsch W (2008) Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 131:3072–3080PubMedPubMedCentralCrossRef
32.
kaishi T, Takahashi T, Nakashima I, Abe M, Ishii T, Aoki M, Fujihara K (2020) Repeated follow-up of AQP4-IgG titer by cell-based assay in neuromyelitis optica spectrum disorders (NMOSD). J Neurol Sci 410:116671
33.
Misu T, Fujihara K, Kakita A, Konno H, Nakamura M, Watanabe S, Takahashi T, Nakashima I, Takahashi H, Itoyama Y (2007) Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis. Brain 130:1224–1234PubMedCrossRef
34.
Aktas O, Smith MA, Rees WA, Bennett JL, She D, Katz E, Cree BAC, group NMs, the NMsi (2021) Serum glial fibrillary acidic protein: a neuromyelitis optica spectrum disorder biomarker. Ann Neurol 89:895–910PubMedPubMedCentralCrossRef
35.
Misu T, Takano R, Fujihara K, Takahashi T, Sato S, Itoyama Y (2009) Marked increase in cerebrospinal fluid glial fibrillar acidic protein in neuromyelitis optica: an astrocytic damage marker. J Neurol Neurosurg Psychiatry 80:575–577PubMedCrossRef
36.
Roemer SF, Parisi JE, Lennon VA, Benarroch EE, Lassmann H, Bruck W, Mandler RN, Weinshenker BG, Pittock SJ, Wingerchuk DM, Lucchinetti CF (2007) Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis. Brain 130:1194–1205PubMedCrossRef
37.
Yonezu T, Ito S, Mori M, Ogawa Y, Makino T, Uzawa A, Kuwabara S (2014) “Bright spotty lesions” on spinal magnetic resonance imaging differentiate neuromyelitis optica from multiple sclerosis. Mult Scler 20:331–337PubMedCrossRef
38.
Fujii C, Itoh K, Saito K, Satoh Y, Makino M, Nakagawa M, Yamaguchi K, Fushiki S, Mizuno T (2018) Persistent microscopic active inflammatory lesions in the central nervous system of a patient with neuromyelitis optica treated with oral prednisolone for more than 40years. eNeurological Sci 11:17-9
39.
Bradl M, Misu T, Takahashi T, Watanabe M, Mader S, Reindl M, Adzemovic M, Bauer J, Berger T, Fujihara K, Itoyama Y, Lassmann H (2009) Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol 66:630–643PubMedCrossRef
40.
Kinoshita M, Nakatsuji Y, Kimura T, Moriya M, Takata K, Okuno T, Kumanogoh A, Kajiyama K, Yoshikawa H, Sakoda S (2009) Neuromyelitis optica: passive transfer to rats by human immunoglobulin. Biochem Biophys Res Commun 386:623–627PubMedCrossRef
41.
Bennett JL, Lam C, Kalluri SR, Saikali P, Bautista K, Dupree C, Glogowska M, Case D, Antel JP, Owens GP, Gilden D, Nessler S, Stadelmann C, Hemmer B (2009) Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica. Ann Neurol 66:617–629PubMedPubMedCentralCrossRef
42.
Saadoun S, Waters P, Bell BA, Vincent A, Verkman AS, Papadopoulos MC (2010) Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice. Brain 133:349–361PubMedPubMedCentralCrossRef
43.
Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P (1994) Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance. Proc Natl Acad Sci U S A 91:13052–13056PubMedPubMedCentralCrossRef
44.
Jin BJ, Rossi A, Verkman AS (2011) Model of aquaporin-4 supramolecular assembly in orthogonal arrays based on heterotetrameric association of M1–M23 isoforms. Biophys J 100:2936–2945PubMedPubMedCentralCrossRef
45.
Nicchia GP, Cogotzi L, Rossi A, Basco D, Brancaccio A, Svelto M, Frigeri A (2008) Expression of multiple AQP4 pools in the plasma membrane and their association with the dystrophin complex. J Neurochem 105:2156–2165PubMedCrossRef
46.
Furman CS, Gorelick-Feldman DA, Davidson KG, Yasumura T, Neely JD, Agre P, Rash JE (2003) Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms. Proc Natl Acad Sci U S A 100:13609–13614PubMedPubMedCentralCrossRef
47.
Takata K, Matsuzaki T, Tajika Y (2004) Aquaporins: water channel proteins of the cell membrane. Prog Histochem Cytochem 39:1–83PubMedCrossRef
48.
Zipfel PF, Skerka C (2009) Complement regulators and inhibitory proteins. Nat Rev Immunol 9:729–740PubMedCrossRef
49.
Yao X, Verkman AS (2017) Complement regulator CD59 prevents peripheral organ injury in rats made seropositive for neuromyelitis optica immunoglobulin G. Acta Neuropathol Commun 5:57PubMedPubMedCentralCrossRef
50.
Soltys J, Liu Y, Ritchie A, Wemlinger S, Schaller K, Schumann H, Owens GP, Bennett JL (2019) Membrane assembly of aquaporin-4 autoantibodies regulates classical complement activation in neuromyelitis optica. J Clin Invest 129:2000–2013PubMedPubMedCentralCrossRef
51.
Sudo A, Chihara N, Takenaka Y, Nakamura T, Ueda T, Sekiguchi K, Toda T (2018) Paraneoplastic NMOSD associated with EG junction adenocarcinoma expressing unprotected AQP4. Neurol Neuroimmunol Neuroinflamm 5:e482PubMedPubMedCentralCrossRef
52.
Mitsui S, Tanaka Y, Kimura K, Jimbo N, Chihara N, Maniwa Y. 2021. Paraneoplastic neuromyelitis optica spectrum disorder associated with atypical thymic carcinoid: a case report. Ann Thorac Cardiovasc Surg
53.
Varrin-Doyer M, Spencer CM, Schulze-Topphoff U, Nelson PA, Stroud RM, Cree BA, Zamvil SS (2012) Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. Ann Neurol 72:53–64PubMedPubMedCentralCrossRef
54.
55.
Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121–1133PubMedCrossRef
56.
Melamed E, Levy M, Waters PJ, Sato DK, Bennett JL, John GR, Hooper DC, Saiz A, Bar-Or A, Kim HJ, Pandit L, Leite MI, Asgari N, Kissani N, Hintzen R, Marignier R, Jarius S, Marcelletti J, Smith TJ, Yeaman MR, Han MH, Aktas O, Apiwattanakul M, Banwell B, Bichuetti D, Broadley S, Cabre P, Chitnis T, De Seze J, Fujihara K, Greenberg B, Hellwig K, Iorio R, Jarius S, Klawiter E, Kleiter I, Lana-Peixoto M, Nakashima OK, Palace J, Paul F, Prayoonwiwat N, Ruprecht K, Stuve O, Tedder T, Tenembaum S, Garrahan JP, Aires B, van Herle K, van Pelt D, Villoslada P, Waubant E, Weinshenker B, Wingerchuk D, Wurfel J, Zamvil S (2015) Update on biomarkers in neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm 2:e134PubMedPubMedCentralCrossRef
57.
Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H (2011) Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34:108–121PubMedPubMedCentralCrossRef
58.
Nicolas P, Ruiz A, Cobo-Calvo A, Fiard G, Giraudon P, Vukusic S, Marignier R (2019) The balance in T follicular helper cell subsets is altered in neuromyelitis optica spectrum disorder patients and restored by rituximab. Front Immunol 10:2686PubMedPubMedCentralCrossRef
59.
Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A et al (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73–76PubMedCrossRef
60.
61.
Uzawa A, Mori M, Arai K, Sato Y, Hayakawa S, Masuda S, Taniguchi J, Kuwabara S (2010) Cytokine and chemokine profiles in neuromyelitis optica: significance of interleukin-6. Mult Scler 16:1443–1452PubMedCrossRef
62.
Barros PO, Cassano T, Hygino J, Ferreira TB, Centuriao N, Kasahara TM, Andrade RM, Linhares UC, Andrade AF, Vasconcelos CC, Alvarenga R, Marignier R, Bento CA (2016) Prediction of disease severity in neuromyelitis optica by the levels of interleukin (IL)-6 produced during remission phase. Clin Exp Immunol 183:480–489PubMedCrossRef
63.
Uzawa A, Mori M, Sato Y, Masuda S, Kuwabara S (2012) CSF interleukin-6 level predicts recovery from neuromyelitis optica relapse. J Neurol Neurosurg Psychiatry 83:339–340PubMedCrossRef
64.
Fujihara K, Bennett JL, de Seze J, Haramura M, Kleiter I, Weinshenker BG, Kang D, Mughal T, Yamamura T. 2020. Interleukin-6 in neuromyelitis optica spectrum disorder pathophysiology. Neurol Neuroimmunol Neuroinflamm 7
65.
Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238PubMedCrossRef
66.
Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB, Oukka M, Kuchroo VK (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448:484–487PubMedPubMedCentralCrossRef
67.
Diehl SA, Schmidlin H, Nagasawa M, Blom B, Spits H (2012) IL-6 triggers IL-21 production by human CD4+ T cells to drive STAT3-dependent plasma cell differentiation in B cells. Immunol Cell Biol 90:802–811PubMedPubMedCentralCrossRef
68.
Molnarfi N, Schulze-Topphoff U, Weber MS, Patarroyo JC, Prod’homme T, Varrin-Doyer M, Shetty A, Linington C, Slavin AJ, Hidalgo J, Jenne DE, Wekerle H, Sobel RA, Bernard CC, Shlomchik MJ, Zamvil SS (2013) MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. J Exp Med 210:2921–37PubMedPubMedCentralCrossRef
69.
Radbruch A, Muehlinghaus G, Luger EO, Inamine A, Smith KG, Dorner T, Hiepe F (2006) Competence and competition: the challenge of becoming a long-lived plasma cell. Nat Rev Immunol 6:741–750PubMedCrossRef
70.
Chihara N, Aranami T, Sato W, Miyazaki Y, Miyake S, Okamoto T, Ogawa M, Toda T, Yamamura T (2011) Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci U S A 108:3701–3706PubMedPubMedCentralCrossRef
71.
Kowarik MC, Astling D, Gasperi C, Wemlinger S, Schumann H, Dzieciatkowska M, Ritchie AM, Hemmer B, Owens GP, Bennett JL (2017) CNS aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder. Ann Clin Transl Neurol 4:369–380PubMedPubMedCentralCrossRef
72.
Matsushita T, Tateishi T, Isobe N, Yonekawa T, Yamasaki R, Matsuse D, Murai H, Kira J (2013) Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis. PLoS ONE 8:e61835PubMedPubMedCentralCrossRef
73.
Chihara N, Aranami T, Oki S, Matsuoka T, Nakamura M, Kishida H, Yokoyama K, Kuroiwa Y, Hattori N, Okamoto T, Murata M, Toda T, Miyake S, Yamamura T (2013) Plasmablasts as migratory IgG-producing cells in the pathogenesis of neuromyelitis optica. PLoS ONE 8:e83036PubMedPubMedCentralCrossRef
74.
75.
Cotzomi E, Stathopoulos P, Lee CS, Ritchie AM, Soltys JN, Delmotte FR, Oe T, Sng J, Jiang R, Ma AK, Vander Heiden JA, Kleinstein SH, Levy M, Bennett JL, Meffre E, O’Connor KC (2019) Early B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production. Brain 142:1598–1615PubMedPubMedCentralCrossRef
76.
Jenks SA, Cashman KS, Zumaquero E, Marigorta UM, Patel AV, Wang X, Tomar D, Woodruff MC, Simon Z, Bugrovsky R, Blalock EL, Scharer CD, Tipton CM, Wei C, Lim SS, Petri M, Niewold TB, Anolik JH, Gibson G, Lee FE, Boss JM, Lund FE, Sanz I (2018) Distinct effector B cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity 49(725–39):e6
77.
Ruschil C, Gabernet G, Lepennetier G, Heumos S, Kaminski M, Hracsko Z, Irmler M, Beckers J, Ziemann U, Nahnsen S, Owens GP, Bennett JL, Hemmer B, Kowarik MC (2020) Specific induction of double negative B cells during protective and pathogenic immune responses. Front Immunol 11:606338PubMedPubMedCentralCrossRef
78.
Wilson R, Makuch M, Kienzler AK, Varley J, Taylor J, Woodhall M, Palace J, Leite MI, Waters P, Irani SR (2018) Condition-dependent generation of aquaporin-4 antibodies from circulating B cells in neuromyelitis optica. Brain 141:1063–1074PubMedPubMedCentralCrossRef
79.
Takeshita Y, Obermeier B, Cotleur AC, Spampinato SF, Shimizu F, Yamamoto E, Sano Y, Kryzer TJ, Lennon VA, Kanda T, Ransohoff RM (2017) Effects of neuromyelitis optica-IgG at the blood-brain barrier in vitro. Neurol Neuroimmunol Neuroinflamm 4:e311PubMedCrossRef
80.
Petkovic F, Lazzarino GP, Engblom D, Blomqvist A (2020) IL-6R expressed on CNS vascular endothelial cells contributes to the development of experimental autoimmune encephalomyelitis in mice. J Neuroimmunol 342:577211PubMedCrossRef
81.
Hinson SR, Roemer SF, Lucchinetti CF, Fryer JP, Kryzer TJ, Chamberlain JL, Howe CL, Pittock SJ, Lennon VA (2008) Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2. J Exp Med 205:2473–2481PubMedPubMedCentralCrossRef
82.
Chen T, Lennon VA, Liu YU, Bosco DB, Li Y, Yi MH, Zhu J, Wei S, Wu LJ (2020) Astrocyte-microglia interaction drives evolving neuromyelitis optica lesion. J Clin Invest 130:4025–4038PubMedPubMedCentral
83.
Mandler RN, Ahmed W, Dencoff JE (1998) Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 51:1219–1220PubMedCrossRef
84.
Jacob A, Matiello M, Weinshenker BG, Wingerchuk DM, Lucchinetti C, Shuster E, Carter J, Keegan BM, Kantarci OH, Pittock SJ (2009) Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol 66:1128–1133PubMedCrossRef
85.
Kitley J, Elsone L, George J, Waters P, Woodhall M, Vincent A, Jacob A, Leite MI, Palace J (2013) Methotrexate is an alternative to azathioprine in neuromyelitis optica spectrum disorders with aquaporin-4 antibodies. J Neurol Neurosurg Psychiatry 84:918–921PubMedCrossRef
86.
Tanaka M, Kinoshita M, Tanaka K (2015) Corticosteroid and tacrolimus treatment in neuromyelitis optica related disorders. Mult Scler 21:669PubMedCrossRef
87.
Kageyama T, Komori M, Miyamoto K, Ozaki A, Suenaga T, Takahashi R, Kusunoki S, Matsumoto S, Kondo T (2013) Combination of cyclosporine A with corticosteroids is effective for the treatment of neuromyelitis optica. J Neurol 260:627–634PubMedCrossRef
88.
Damato V, Evoli A, Iorio R (2016) Efficacy and safety of rituximab therapy in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis. JAMA Neurol 73:1342–1348PubMedCrossRef
89.
Thomas TC, Rollins SA, Rother RP, Giannoni MA, Hartman SL, Elliott EA, Nye SH, Matis LA, Squinto SP, Evans MJ (1996) Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol 33:1389–1401PubMedCrossRef
90.
Hinson SR, Romero MF, Popescu BF, Lucchinetti CF, Fryer JP, Wolburg H, Fallier-Becker P, Noell S, Lennon VA (2012) Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci U S A 109:1245–1250PubMedCrossRef
91.
Duan T, Smith AJ, Verkman AS (2018) Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica. J Neuroinflammation 15:294PubMedPubMedCentralCrossRef
92.
93.
Piatek P, Domowicz M, Lewkowicz N, Przygodzka P, Matysiak M, Dzitko K, Lewkowicz P (2018) C5a-preactivated neutrophils are critical for autoimmune-induced astrocyte dysregulation in neuromyelitis optica spectrum disorder. Front Immunol 9:1694PubMedPubMedCentralCrossRef
94.
Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, O’Toole O, Wingerchuk DM (2013) Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol 12:554–562PubMedCrossRef
95.
Wingerchuk DM, Fujihara K, Palace J, Berthele A, Levy M, Kim HJ, Nakashima I, Oreja-Guevara C, Wang KC, Miller L, Shang S, Sabatella G, Yountz M, Pittock SJ, Group PS (2021) Long-term safety and efficacy of eculizumab in aquaporin-4 IgG-positive NMOSD. Ann Neurol 89:1088–98PubMedPubMedCentralCrossRef
96.
Igawa T, Ishii S, Tachibana T, Maeda A, Higuchi Y, Shimaoka S, Moriyama C, Watanabe T, Takubo R, Doi Y, Wakabayashi T, Hayasaka A, Kadono S, Miyazaki T, Haraya K, Sekimori Y, Kojima T, Nabuchi Y, Aso Y, Kawabe Y, Hattori K (2010) Antibody recycling by engineered pH-dependent antigen binding improves the duration of antigen neutralization. Nat Biotechnol 28:1203–7PubMedCrossRef
97.
Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T (2013) Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Mod Rheumatol 23:827–831PubMedCrossRef
98.
Ayzenberg I, Kleiter I, Schroder A, Hellwig K, Chan A, Yamamura T, Gold R (2013) Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy. JAMA Neurol 70:394–397PubMedCrossRef
99.
Araki M, Matsuoka T, Miyamoto K, Kusunoki S, Okamoto T, Murata M, Miyake S, Aranami T, Yamamura T (2014) Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica: a pilot study. Neurology 82:1302–1306PubMedPubMedCentralCrossRef
100.
Zhang C, Zhang M, Qiu W, Ma H, Zhang X, Zhu Z, Yang CS, Jia D, Zhang TX, Yuan M, Feng Y, Yang L, Lu W, Yu C, Bennett JL, Shi FD, Investigators TS (2020) Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol 19:391–401PubMedPubMedCentralCrossRef
101.
Palanichamy A, Jahn S, Nickles D, Derstine M, Abounasr A, Hauser SL, Baranzini SE, Leppert D, von Budingen HC (2014) Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J Immunol 193:580–586PubMedCrossRef
102.
Krumbholz M, Derfuss T, Hohlfeld R, Meinl E (2012) B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol 8:613–623PubMedCrossRef
103.
Evens AM, Jovanovic BD, Su YC, Raisch DW, Ganger D, Belknap SM, Dai MS, Chiu BC, Fintel B, Cheng Y, Chuang SS, Lee MY, Chen TY, Lin SF, Kuo CY (2011) Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports. Ann Oncol 22:1170–1180PubMedCrossRef
104.
Rensel M, Zabeti A, Mealy MA, Cimbora D, She D, Drappa J, Katz E. 2021. Long-term efficacy and safety of inebilizumab in neuromyelitis optica spectrum disorder: analysis of aquaporin-4-immunoglobulin G-seropositive participants taking inebilizumab for 4 years in the N-MOmentum trial. Mult Scler: 13524585211047223
Metadata
Title
Immuno-pathogenesis of neuromyelitis optica and emerging therapies
Authors
Norio Chihara
Takashi Yamamura
Publication date
30-05-2022
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 5/2022
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-022-00941-9

Other articles of this Issue 5/2022

Seminars in Immunopathology 5/2022 Go to the issue

Correction

Correction to: Establishment of tissue-resident immune populations in the fetus

Review

A Conceptual Framework for Inducing T Cell-Mediated Immunity Against Glioblastoma

Review

Cell death in development, maintenance, and diseases of the nervous system

Correction

Correction to: Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation

Review

Narcolepsy: a model interaction between immune system, nervous system, and sleep-wake regulation

Review

Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits