{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T06:16:27Z","timestamp":1764656187718,"version":"build-2065373602"},"reference-count":91,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuromyelitis optica (NMO) is a rare disease usually presenting with bilateral or unilateral optic neuritis with simultaneous or sequential transverse myelitis. Autoantibodies directed against aquaporin-4 (AQP4-IgG) are found in most patients. They are believed to cross the blood\u2013brain barrier, target astrocytes, activate complement, and eventually lead to astrocyte destruction, demyelination, and axonal damage. However, it is still not clear what the primary pathological event is. We hypothesize that the interaction of AQP4-IgG and astrocytes leads to DNA damage and apoptosis. We studied the effect of sera from seropositive NMO patients and healthy controls (HCs) on astrocytes\u2019 immune gene expression and viability. We found that sera from seropositive NMO patients led to higher expression of apoptosis-related genes, including BH3-interacting domain death agonist (BID), which is the most significant differentiating gene (p &lt; 0.0001), and triggered more apoptosis in astrocytes compared to sera from HCs. Furthermore, NMO sera increased DNA damage and led to a higher expression of immunological genes that interact with BID (TLR4 and NOD-1). Our findings suggest that sera of seropositive NMO patients might cause astrocytic DNA damage and apoptosis. It may be one of the mechanisms implicated in the primary pathological event in NMO and provide new avenues for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms23137117","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T22:31:14Z","timestamp":1656369074000},"page":"7117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sera of Neuromyelitis Optica Patients Increase BID-Mediated Apoptosis in Astrocytes"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8878-4211","authenticated-orcid":false,"given":"Omri","family":"Zveik","sequence":"first","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroimmunology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0968-3576","authenticated-orcid":false,"given":"Ariel","family":"Rechtman","sequence":"additional","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroimmunology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-2184","authenticated-orcid":false,"given":"Nitzan","family":"Haham","sequence":"additional","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroimmunology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irit","family":"Adini","sequence":"additional","affiliation":[{"name":"Department of Surgery, Harvard Medical School, Center for Engineering in Medicine & Surgery, Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamar","family":"Canello","sequence":"additional","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroimmunology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-1573","authenticated-orcid":false,"given":"Iris","family":"Lavon","sequence":"additional","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroimmunology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livnat","family":"Brill","sequence":"additional","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroimmunology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adi","family":"Vaknin-Dembinsky","sequence":"additional","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroimmunology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1474-4422(13)70259-X","article-title":"Optic neuritis","volume":"13","author":"Toosy","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1001\/archopht.1991.01080120057025","article-title":"The Clinical Profile of Optic Neuritis","volume":"109","author":"Beck","year":"1991","journal-title":"Arch. 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