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Binding of these antibodies to AQP4 on astrocytes initiates damage to these cells, which culminates in the formation of large tissue destructive lesions in the central nervous system (CNS). Consequently, untreated patients may become permanently blind or paralyzed. Studies on the induction and breakage of tolerance to AQP4 could be of great benefit for NMOSD patients. So far, however, all attempts to create suitable animal models by active sensitization have failed. We addressed this challenge and identified peptides, which mimic the conformational AQP4 epitopes recognized by pathogenic antibodies of NMOSD patients. Here we show that these mimotopes can induce the production of AQP4-reactive antibodies in Lewis rats. Hence, our results provide a conceptual framework for the formation of such antibodies in NMOSD patients, and aid to improve immunization strategies for the creation of animal models suitable for tolerance studies in this devastating disease.<\/jats:p>","DOI":"10.1186\/s40478-020-00920-x","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T12:02:37Z","timestamp":1586952157000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes"],"prefix":"10.1186","volume":"8","author":[{"given":"Irina","family":"Tsymala","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalini","family":"Nigritinou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bleranda","family":"Zeka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rouven","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Niederschick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Matkovi\u0107","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel J.","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Szalay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Schanda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Lerch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuro","family":"Misu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Fujihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Dahle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Pache","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulus","family":"Rommer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fritz","family":"Leutmezer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsolt","family":"Illes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Isabel","family":"Leite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Palace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Scholze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Reindl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Lassmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Bradl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"920_CR1","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1084\/jem.20050304","volume":"202","author":"VA Lennon","year":"2005","unstructured":"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. 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JP is partly funded by highly specialised services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmun, MedDay, Abide ARGENX, UCB and Viela Bio and grants from Merck Serono, Novartis, Biogen Idec, Teva, Abide, MedImmune, Bayer Schering, Genzyme, Chugai and Alexion. She has received grants from the MS society, Guthie Jackson Foundation, NIHR, Oxford Health Services Research Committee, EDEN, MRC, GMSI, John Fell and Myaware for research studies. KF reports personal fees from Alexion, Asahi Kasei Medical, Bayer, Biogen, Chugai\/Roche, Dainihon Sumitomo, Eisai, MedImmune\/VielaBio, Mitsubishi-Tanabe, Novartis, Ono, Takeda and Teijin, during the conduct of the study; grants from Ministry of Education, Science and Technology of Japan and Ministry of Health, Welfare and Labor of Japan. ZI has received honoraria for clinical endpoint committees in clinical trials of NMOSD; has served on scientific advisory board, has received honoraria for lecturing, and has received support for congress participation from Biogen, Sanofi-Genzyme, Merck, Teva, Roche, and Novartis, respectively. MIL reported being involved in aquaporin 4 testing, and is partially supported by NHS England highly specialised commissioning group for neuromyelitis. MIL has received support for scientific meetings from Novartis and Biogen Idec and honorarium for lectures and advisory work from Biogen Idec, Viela Bio and Argenx. She has received research fellowships from NIHR, University of Oxford and Myaware. MR, KS declare that the University Hospital and Medical University of Innsbruck (Austria) receives payments for antibody assays (MOG, AQP4, and other autoantibodies) and for MOG and AQP4 antibody validation experiments organized by Euroimmun (L\u00fcbeck, Germany).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"49"}}