{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:34:17Z","timestamp":1786977257675,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8J1081"],"award-info":[{"award-number":["CMRPG8J1081"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8K1111"],"award-info":[{"award-number":["CMRPG8K1111"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8K111"],"award-info":[{"award-number":["CMRPG8K111"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["2"],"award-info":[{"award-number":["2"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8K0632"],"award-info":[{"award-number":["CMRPG8K0632"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8L1331"],"award-info":[{"award-number":["CMRPG8L1331"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Autoimmune encephalitis (AE) is caused by autoantibodies attacking neuronal cell surface antigens and\/or synaptic antigens. We previously demonstrated that\n                      <jats:italic>S100A6<\/jats:italic>\n                      was hypomethylated in patients with AE and that it promoted B lymphocyte infiltration through the simulated blood\u2013brain barrier (BBB). In this study, we focused on the epigenetic regulation of\n                      <jats:italic>S100A6<\/jats:italic>\n                      , the process by which S100A6 affects B lymphocyte infiltration, and the therapeutic potential of S100A6 antibodies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We enrolled and collected serum from 10 patients with AE and 10 healthy control (HC) subjects. Promoter methylation and 5\u2010azacytidine treatment assays were conducted to observe the methylation process of\n                      <jats:italic>S100A6<\/jats:italic>\n                      . The effect of S100A6 on B lymphocytes was analyzed using an adhesion assay and leukocyte transendothelial migration (LTEM) assay. A LTEM assay was also used to compare the effects of the serum of HCs, serum of AE patients, S100A6 recombinant protein, and S100A6 antibodies on B lymphocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      The promoter methylation and 5\u2010azacytidine treatment assays confirmed that\n                      <jats:italic>S100A6<\/jats:italic>\n                      was regulated by DNA methylation. The adhesion study demonstrated that the addition of S100A6 enhanced adhesion between B lymphocytes and a BBB endothelial cell line in a concentration\u2010dependent manner. The LTEM assay showed that the serum of AE patients, as well as S100A6, promoted B lymphocyte infiltration and that this effect could be attenuated by S100A6 antibodies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We clarified that S100A6 was under epigenetic regulation in patients with AE and that it helped B lymphocytes to adhere to and infiltrate the BBB endothelial layer, which could be counteracted by S100A6 antibodies. Therefore, the methylation profile of\n                      <jats:italic>S100A6<\/jats:italic>\n                      could be a marker of the activity of AE, and countering the effect of S100A6 may be a potential treatment target for AE.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.2897","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T08:32:52Z","timestamp":1675758772000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["S100A6 participates in initiation of autoimmune encephalitis and is under epigenetic control"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1193-4485","authenticated-orcid":false,"given":"Chih\u2010Hsiang","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurology Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine  Kaohsiung 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