{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:44:47Z","timestamp":1793285087477,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["SMARTAGE 01GQ1420A"],"award-info":[{"award-number":["SMARTAGE 01GQ1420A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Association","doi-asserted-by":"publisher","award":["Exc 257"],"award-info":[{"award-number":["Exc 257"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Association","doi-asserted-by":"publisher","award":["PR 1274\/2\u20101"],"award-info":[{"award-number":["PR 1274\/2\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Association","doi-asserted-by":"publisher","award":["PR 1274\/3\u20101"],"award-info":[{"award-number":["PR 1274\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Association","doi-asserted-by":"publisher","award":["SFB 1315"],"award-info":[{"award-number":["SFB 1315"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Association","doi-asserted-by":"publisher","award":["SFB 958"],"award-info":[{"award-number":["SFB 958"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Association","doi-asserted-by":"publisher","award":["SPP 1665"],"award-info":[{"award-number":["SPP 1665"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Association","doi-asserted-by":"publisher","award":["FOR 3004"],"award-info":[{"award-number":["FOR 3004"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001656","name":"Helmholtz Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001656","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["17H03678"],"award-info":[{"award-number":["17H03678"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["19H03331"],"award-info":[{"award-number":["19H03331"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["19K22548"],"award-info":[{"award-number":["19K22548"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Leucine\u2010rich glioma\u2010inactivated 1 (LGI1) encephalitis is the second most common antibody\u2010mediated encephalopathy, but insight into the intrathecal B\u2010cell autoimmune response, including clonal relationships, isotype distribution, frequency, and pathogenic effects of single LGI1 antibodies, has remained limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We cloned, expressed, and tested antibodies from 90 antibody\u2010secreting cells (ASCs) and B cells from the cerebrospinal fluid (CSF) of several patients with LGI1 encephalitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty\u2010four percent of the ASCs and 21% of the memory B cells encoded LGI1\u2010reactive antibodies, whereas reactivities to other brain epitopes were rare. All LGI1 antibodies were of IgG1, IgG2, or IgG4 isotype and had undergone affinity maturation. Seven of the overall 26 LGI1 antibodies efficiently blocked the interaction of LGI1 with its receptor ADAM22 in vitro, and their mean LGI1 signal on mouse brain sections was weak compared to the remaining, non\u2013ADAM22\u2010competing antibodies. Nevertheless, both types of LGI1 antibodies increased the intrinsic cellular excitability and glutamatergic synaptic transmission of hippocampal CA3 neurons in slice cultures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Our data show that the patients\u2019 intrathecal B\u2010cell autoimmune response is dominated by LGI1 antibodies and that LGI1 antibodies alone are sufficient to promote neuronal excitability, a basis of seizure generation. Fundamental differences in target specificity and antibody hypermutations compared to the CSF autoantibody repertoire in N\u2010methyl\u2010D\u2010aspartate receptor encephalitis underline the clinical concept that autoimmune encephalitides are very distinct entities.\n                      <jats:bold>Ann Neurol 2020;87:405\u2013418<\/jats:bold>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25666","type":"journal-article","created":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T01:04:30Z","timestamp":1578099870000},"page":"405-418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":133,"title":["Human Cerebrospinal Fluid Monoclonal LGI1 Autoantibodies Increase Neuronal Excitability"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4187-7549","authenticated-orcid":false,"given":"Hans\u2010Christian","family":"Kornau","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin  Berlin Germany"},{"name":"Neuroscience Research Center, Cluster NeuroCure, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-1015","authenticated-orcid":false,"given":"Jakob","family":"Kreye","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin  Berlin Germany"},{"name":"Department of Neurology and Experimental Neurology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Department of Pediatric Neurology Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-6970","authenticated-orcid":false,"given":"Alexander","family":"Stumpf","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Cluster NeuroCure, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7724-8643","authenticated-orcid":false,"given":"Yuko","family":"Fukata","sequence":"additional","affiliation":[{"name":"Division of Membrane Physiology, Department of Molecular and Cellular Physiology National Institute for Physiological Sciences, National Institutes of Natural Sciences  Okazaki Japan"},{"name":"Department of Physiological Sciences School of Life Science, SOKENDAI, Graduate University for Advanced Studies  Okazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8775-024X","authenticated-orcid":false,"given":"Daniel","family":"Parthier","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Cluster NeuroCure, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna P.","family":"Sammons","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Cluster NeuroCure, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Imbrosci","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Cluster NeuroCure, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4441-1648","authenticated-orcid":false,"given":"Sarah","family":"Kurpjuweit","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin  Berlin Germany"},{"name":"Department of Neurology and Experimental Neurology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander B.","family":"Kowski","sequence":"additional","affiliation":[{"name":"Department of Neurology and Experimental Neurology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5200-9806","authenticated-orcid":false,"given":"Masaki","family":"Fukata","sequence":"additional","affiliation":[{"name":"Division of Membrane Physiology, Department of Molecular and Cellular Physiology National Institute for Physiological Sciences, National Institutes of Natural Sciences  Okazaki Japan"},{"name":"Department of Physiological Sciences School of Life Science, SOKENDAI, Graduate University for Advanced Studies  Okazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-7976","authenticated-orcid":false,"given":"Harald","family":"Pr\u00fcss","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin  Berlin Germany"},{"name":"Department of Neurology and Experimental Neurology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Schmitz","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin  Berlin Germany"},{"name":"Neuroscience Research Center, Cluster NeuroCure, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Einstein Center for Neurosciences  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq213"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70137-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00010.2016"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.43"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2015.27"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1708712"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22307"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.4226"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.561"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy109"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24860"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24858"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25216"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129947"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03947-w"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1511910112"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.01.033"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq047"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914537107"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq171"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618656114"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02756.x"},{"key":"e_1_2_8_24_1","first-page":"3144","article-title":"LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory","volume":"141","author":"Petit\u2010Pedrol M","year":"2018","journal-title":"Brain"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50919"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww208"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.444"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2007.09.017"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086907"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aap8029"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25460"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3506-13.2013"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4161"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri706"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003009"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23577"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/336379a0"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.127068"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-17-06553.2001"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24545"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12939"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2015.06.008"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00164-1"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.07.031"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx323"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1992.tb00155.x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-21-08246.1997"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21769"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0167-10.2010"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21589"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.25666","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25666","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.25666","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25666","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T22:47:14Z","timestamp":1694040434000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.25666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,27]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/ana.25666"],"URL":"https:\/\/doi.org\/10.1002\/ana.25666","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,27]]},"assertion":[{"value":"2019-04-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}