{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:13:49Z","timestamp":1784740429044,"version":"3.55.0"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>This study aimed to compare clinical outcomes in NMOSD patients with non-AQP4-IgG autoantibodies, specifically anti-connective tissue disease antibodies (anti-CTD Abs) and antithyroid antibodies (ATAbs), to evaluate their impact on disease severity and prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective analysis was conducted using data from NMOSD inpatients with follow-up periods \u2265180\u202fdays, stratified by antibody status: anti-CTD Abs (+)\/(\u2212), ATAbs (+)\/(\u2212), or double positivity (+)\/(\u2212). The primary outcomes included relapse rates, Expanded Disability Status Scale (EDSS) scores, and survival outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(1) Anti-CTD Abs (+): higher proportion of female patients, increased relapse frequency; decreased red blood cell (RBC) count and aspartate aminotransferase (AST) levels. (2) ATAbs (+): greater incidence of acute brainstem syndrome (ABS); reduced peripheral leukocyte, neutrophil, and lymphocyte counts; elevated serum urea levels. (3) Double (+): marked female predominance, higher incidence of ABS, decreased RBC count, hemoglobin (Hb) levels, and cerebrospinal fluid (CSF) chloride concentration; elevated serum urea. (4) AQP4-IgG association: AQP4-IgG-positive patients were more frequently female, with higher prevalence of anti-CTD Abs positivity but lower prevalence of ATAbs positivity. (5) Prognostic analysis: both double-positive and single-antibody-positive groups showed higher disability (EDSS \u22654.0\/\u22656.0) compared with antibody-negative patients, although no significant differences were observed between the two single-antibody subgroups. (6) Multivariate analysis identified combined antibody positivity (OR\u202f=\u202f16.292), baseline EDSS score (OR\u202f=\u202f3.179), and age at onset (OR\u202f=\u202f1.052) as independent predictors of poor clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Routine screening for anti-CTD Abs and ATAbs in NMOSD patients may aid in assessing disease severity and prognosis. Patients with double positivity represent a high-risk subgroup requiring aggressive therapeutic strategies to prevent severe disability.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1634127","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T04:13:03Z","timestamp":1756181583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical features and prognosis of NMOSD patients with positive autoimmune antibodies"],"prefix":"10.3389","volume":"16","author":[{"given":"Yutao","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.5603\/pjnns.100945","article-title":"Update on diagnosis and treatment of neuromyelitis optica spectrum disorders (NMOSD)\u2014recommendations of section of multiple sclerosis and Neuroimmunology of polish neurological society","volume":"59","author":"Zakrzewska Pniewska","year":"2025","journal-title":"Neurol Neurochir Pol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"103465","DOI":"10.1016\/j.autrev.2023.103465","article-title":"A comprehensive review of the advances in neuromyelitis optica spectrum disorder","volume":"22","author":"Siriratnam","year":"2023","journal-title":"Autoimmun Rev"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s11926-021-01000-2","article-title":"Neuromyelitis optica spectrum disorders (NMOSD) and connective tissue disease (CTD): an update for the rheumatologist","volume":"23","author":"Cruz","year":"2021","journal-title":"Curr Rheumatol Rep"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"7525","DOI":"10.1007\/s00415-024-12698-2","article-title":"Aquaporin4-IgG seropositivity significantly increases the risk of comorbid autoimmune diseases in NMOSD patients: population-based registry data","volume":"271","author":"Pekmezovic","year":"2024","journal-title":"J Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s13760-019-01176-6","article-title":"Frequency of autoimmune disorders and autoantibodies in European patients with neuromyelitis optica spectrum disorders","volume":"120","author":"Gkaniatsou","year":"2020","journal-title":"Acta Neurol Belg"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"103425","DOI":"10.1016\/j.msard.2021.103425","article-title":"Positive antithyroid antibody predicts severity of neuromyelitis optica spectrum disorder in children","volume":"57","author":"Huo","year":"2022","journal-title":"Mult Scler Relat Disord"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"578151","DOI":"10.1016\/j.jneuroim.2023.578151","article-title":"Serum antinuclear antibodies associate with severe disease activity in neuromyelitis optica spectrum disorder","volume":"382","author":"Wang","year":"2023","journal-title":"J Neuroimmunol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneuroim.2018.11.012","article-title":"The clinical and prognostic value of antinuclear antibodies in NMO-IgG seropositive neuromyelitis optica spectrum disorder","volume":"328","author":"Lee","year":"2019","journal-title":"J Neuroimmunol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3341","DOI":"10.1007\/s00415-023-11634-0","article-title":"Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD)\u2013revised recommendations of the Neuromyelitis Optica study group (NEMOS). 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