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Binding of NMO\u2010IgG to aquaporin\u20104 expressed in end\u2010feet of astrocytes leads to complement\u2010dependent disruption of astrocytes followed by demyelination. One therapeutic option for NMO is to prevent the binding of NMO\u2010IgG to aquaporin\u20104, using high\u2010avidity, non\u2010pathogenic\u2013chimeric, monoclonal antibodies to this water channel. We describe here the development of such antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>cDNAs encoding variable regions of heavy and light chains of monoclonal antibodies against the extracellular domains of human aquaporin\u20104 were cloned from hybridoma total RNA and fused to those encoding constant regions of human IgG1 and Ig\u03ba respectively. Then mammalian expression vectors were constructed to establish stable cell lines secreting mature chimeric antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Original monoclonal antibodies showed high avidity binding to human aquaporin\u20104, as determined by ELISA. Live imaging using Alexa\u2010Fluor\u2010555\u2010labelled antibodies revealed that the antibody D15107 more rapidly bound to cells expressing human aquaporin\u20104 than others and strongly enhanced endocytosis of this water channel, while D12092 also bound rapidly to human aquaporin\u20104 but enhanced endocytosis to a lesser degree. Chimeric D15107 prevented complement\u2010dependent cytotoxicity induced by NMO\u2010IgG from patient sera <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>We have established non\u2010pathogenic, high\u2010avidity, chimeric antibodies against the extracellular domains of human aquaporin\u20104, which provide a novel therapeutic option for preventing the progress and recurrence of NMO\/NMO spectrum disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13340","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T17:25:52Z","timestamp":1443029152000},"page":"103-114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin\u20104 competing with the neuromyelitis optica autoantibody, NMO\u2010IgG"],"prefix":"10.1111","volume":"173","author":[{"given":"Kaori","family":"Miyazaki\u2010Komine","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine Keio University  35 Shinanomachi, Shinjuku\u2010ku Tokyo 160\u20108582 Japan"},{"name":"Department of Orthopaedic Surgery, School of Medicine Keio University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Neurology Tohoku University School of Medicine  1\u20101 Seiryomachi, Aoba\u2010ku Sendai 980\u20108574 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine Keio University  35 Shinanomachi, Shinjuku\u2010ku Tokyo 160\u20108582 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Kusano\u2010Arai","sequence":"additional","affiliation":[{"name":"Quantitative Biology and Medicine, Research Center for Advanced Science and Technology The University of Tokyo  4\u20106\u20101 Komaba, Meguro\u2010ku Tokyo 153\u20108904 Japan"},{"name":"Institute of Immunology Co., Ltd.  1\u20101\u201010 Koraku, Bunkyo\u2010ku Tokyo 112\u20100004 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Iwanari","sequence":"additional","affiliation":[{"name":"Quantitative Biology and Medicine, Research Center for Advanced Science and Technology The University of Tokyo  4\u20106\u20101 Komaba, Meguro\u2010ku Tokyo 153\u20108904 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuro","family":"Misu","sequence":"additional","affiliation":[{"name":"Department of Multiple Sclerosis Therapeutics Tohoku University Graduate School of Medicine  1\u20101 Seiryomachi, Aoba\u2010ku Sendai 980\u20108574 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsushi","family":"Koda","sequence":"additional","affiliation":[{"name":"Research and Development Division Perseus Proteomics Inc.  4\u20107\u20106 Komaba, Meguro\u2010ku Tokyo 153\u20100041 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuyuki","family":"Mitomo","sequence":"additional","affiliation":[{"name":"Research and Development Division Perseus Proteomics Inc.  4\u20107\u20106 Komaba, Meguro\u2010ku Tokyo 153\u20100041 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiko","family":"Sakihama","sequence":"additional","affiliation":[{"name":"Quantitative Biology and Medicine, Research Center for Advanced Science and Technology The University of Tokyo  4\u20106\u20101 Komaba, Meguro\u2010ku Tokyo 153\u20108904 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