{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:46:54Z","timestamp":1780098414006,"version":"3.54.0"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The family Olinder-Nielsen\u00e2\u20ac\u2122s foundation"},{"name":"The Swedish state","award":["ALFGBG-1005059"],"award-info":[{"award-number":["ALFGBG-1005059"]}]},{"name":"The Swedish state","award":["ALFGBG-1005059"],"award-info":[{"award-number":["ALFGBG-1005059"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Tick-borne encephalitis is a viral infection of the central nervous system that may cause severe illness and long-term sequelae, to which underlying mechanisms are not completely understood. Autoantibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) may be triggered by immunologic events, occur sporadically, and can cause autoimmune encephalitis. Following herpes simplex encephalitis and Japanese encephalitis, anti-NMDAR autoantibodies may develop and have been associated with relapse or impaired cognitive recovery. Tick-borne encephalitis has been shown to trigger anti-NMDAR encephalitis in sporadic cases, but the frequency of autoimmunization is unknown.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>The objective of this study was to assess the frequency of intrathecal anti-NMDAR antibody development following tick-borne encephalitis and to explore whether such antibodies could be relevant to cognitive complaints.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Adult patients with tick-borne encephalitis were included retrospectively from one cohort and prospectively from another. A stored post-acute cerebrospinal fluid sample was required for anti-NMDAR analysis. Two commercial kits (Euroimmun AG, L\u00fcbeck, Germany) were used to detect anti-NMDAR IgG antibodies in cerebrospinal fluid.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 71 cerebrospinal fluid samples from 53 patients were analyzed for anti-NMDAR antibodies. Samples were obtained at a median of 91 days (range 21\u2013471) after onset of central nervous system symptoms. Anti-NMDAR antibodies were detected in two samples from a single tick-borne encephalitis patient, corresponding to 1.9% of patients (95% CI: 0.05\u201310.1%).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The development of intrathecal anti-NMDAR autoantibodies following tick-borne encephalitis is a rare event, and further studies are needed to clarify their potential relevance to cognitive outcomes in a minority of cases. Testing for anti-NMDAR antibodies in cerebrospinal fluid may be considered in patients who experience clinical deterioration following an initial recovery.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0334438","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T17:21:56Z","timestamp":1760376116000},"page":"e0334438","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low frequency of N-methyl-D-aspartate receptor autoimmunity in tick-borne encephalitis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2888-2722","authenticated-orcid":true,"given":"Jakob","family":"Mor\u00e9n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbro","family":"Persson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"S\u00f6rman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5ke","family":"Lundkvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanin","family":"Shihab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Studahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Veje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"G\u00fcnther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Westman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"issue":"9627","key":"pone.0334438.ref001","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/S0140-6736(08)60800-4","article-title":"Tick-borne encephalitis","volume":"371","author":"L Lindquist","year":"2008","journal-title":"Lancet"},{"key":"pone.0334438.ref002","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2019.01.014","article-title":"Tick-borne encephalitis in Europe and Russia: Review of pathogenesis, clinical features, therapy, and vaccines","volume":"164","author":"D Ruzek","year":"2019","journal-title":"Antiviral Res"},{"issue":"9","key":"pone.0334438.ref003","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s00705-023-05835-1","article-title":"Renaming of the genus Flavivirus to Orthoflavivirus and extension of binomial species names within the family Flaviviridae","volume":"168","author":"TS Postler","year":"2023","journal-title":"Arch Virol"},{"issue":"10","key":"pone.0334438.ref004","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1111\/ene.13356","article-title":"EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis","volume":"24","author":"P Taba","year":"2017","journal-title":"Eur J Neurol"},{"issue":"7","key":"pone.0334438.ref005","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1007\/s10096-024-04855-2","article-title":"Clinical characteristics and factors affecting disease severity in hospitalized tick-borne encephalitis patients in Norway from 2018 to 2022","volume":"43","author":"H Skudal","year":"2024","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"3","key":"pone.0334438.ref006","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/QCO.0000000000000924","article-title":"Tick-borne encephalitis","volume":"36","author":"N Johnson","year":"2023","journal-title":"Curr Opin Infect Dis"},{"issue":"4","key":"pone.0334438.ref007","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s004150050077","article-title":"Tick-bone encephalitis in Sweden in relation to aseptic meningo-encephalitis of other etiology: a prospective study of clinical course and outcome","volume":"244","author":"G G\u00fcnther","year":"1997","journal-title":"J Neurol"},{"issue":"2","key":"pone.0334438.ref008","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ttbdis.2017.12.001","article-title":"The long-term outcome of tick-borne encephalitis in Central Europe","volume":"9","author":"P Bogovi\u010d","year":"2018","journal-title":"Ticks Tick Borne Dis"},{"issue":"5","key":"pone.0334438.ref009","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s15010-023-02023-w","article-title":"Recovery and sequelae in 523 adults and children with tick-borne encephalitis in Germany","volume":"51","author":"TM Nygren","year":"2023","journal-title":"Infection"},{"issue":"6","key":"pone.0334438.ref010","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/ane.12561","article-title":"Tick-Borne Encephalitis sequelae at long-term follow-up: a self-reported case-control study","volume":"134","author":"M Veje","year":"2016","journal-title":"Acta Neurol Scand"},{"issue":"1","key":"pone.0334438.ref011","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/ana.21050","article-title":"Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma","volume":"61","author":"J Dalmau","year":"2007","journal-title":"Ann Neurol"},{"issue":"12","key":"pone.0334438.ref012","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(08)70224-2","article-title":"Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies","volume":"7","author":"J Dalmau","year":"2008","journal-title":"Lancet Neurol"},{"issue":"9","key":"pone.0334438.ref013","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1056\/NEJMra1708712","article-title":"Antibody-Mediated Encephalitis","volume":"378","author":"J Dalmau","year":"2018","journal-title":"N Engl J Med"},{"key":"pone.0334438.ref014","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2147\/IJGM.S397429","article-title":"Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management Strategies","volume":"16","author":"L Nguyen","year":"2023","journal-title":"Int J Gen Med"},{"issue":"6","key":"pone.0334438.ref015","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1002\/ana.23689","article-title":"N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis","volume":"72","author":"H Pr\u00fcss","year":"2012","journal-title":"Ann Neurol"},{"issue":"18","key":"pone.0334438.ref016","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1212\/WNL.0b013e3182a9f531","article-title":"Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report","volume":"81","author":"F Leypoldt","year":"2013","journal-title":"Neurology"},{"issue":"8","key":"pone.0334438.ref017","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.cmi.2020.09.031","article-title":"Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis","volume":"27","author":"G Westman","year":"2021","journal-title":"Clin Microbiol Infect"},{"key":"pone.0334438.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2019.03.011","article-title":"Anti-NMDAR encephalitis preceded by non-herpetic central nervous system infection: Systematic literature review and first case of tick-borne encephalitis triggering anti-NMDAR encephalitis","volume":"332","author":"E Cavaliere","year":"2019","journal-title":"J Neuroimmunol"},{"issue":"2","key":"pone.0334438.ref019","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.braindev.2019.09.003","article-title":"Japanese encephalitis-induced anti-N-methyl-d-aspartate receptor encephalitis: A hospital-based prospective study","volume":"42","author":"J Ma","year":"2020","journal-title":"Brain Dev"},{"key":"pone.0334438.ref020","doi-asserted-by":"crossref","first-page":"117394","DOI":"10.1016\/j.jns.2021.117394","article-title":"Autoimmune encephalitis after Japanese encephalitis in children: A prospective study","volume":"424","author":"B Liu","year":"2021","journal-title":"J Neurol Sci"},{"issue":"2","key":"pone.0334438.ref021","doi-asserted-by":"crossref","first-page":"102292","DOI":"10.1016\/j.ttbdis.2023.102292","article-title":"Tick-borne encephalitis as a trigger for anti-N-Methyl-d-aspartate receptor encephalitis","volume":"15","author":"TA Gaist","year":"2024","journal-title":"Ticks Tick Borne Dis"},{"key":"pone.0334438.ref022","unstructured":"Gri\u0161ka V, Veje M, Pakalnien\u0117 J, Studahl M, Mickien\u0117 A. Autoimmune encephalitis antibody detection in patients with persistent or progressing sequelae after tick-borne encephalitis [E-poster] [Internet]. 2022 [cited 2025 Apr 25]. Available from: https:\/\/hdl.handle.net\/20.500.12512\/243573"},{"issue":"2","key":"pone.0334438.ref023","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1474-4422(13)70282-5","article-title":"Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study","volume":"13","author":"N Gresa-Arribas","year":"2014","journal-title":"Lancet Neurol"},{"key":"pone.0334438.ref024","unstructured":"The European Commission. COMMISSION IMPLEMENTING DECISION (EU) 2018\/ 945 - of 22 June 2018 - on the communicable diseases and related special health issues to be covered by epidemiological surveillance as well as relevant case definitions [Internet]. June 22, 2018. Available from: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/PDF\/?uri=CELEX:32018D0945&from=EN#page=45"},{"issue":"11","key":"pone.0334438.ref025","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.cmi.2016.07.028","article-title":"N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis","volume":"22","author":"G Westman","year":"2016","journal-title":"Clin Microbiol Infect"},{"key":"pone.0334438.ref026","author":"R Core Team","year":"2023"},{"key":"pone.0334438.ref027","author":"Posit Team","year":"2023"},{"key":"pone.0334438.ref028","unstructured":"Dorai-Raj S. binom: Binomial Confidence Intervals for Several Parameterizations [Internet]. 2022. Available from: https:\/\/CRAN.R-project.org\/package=binom"},{"key":"pone.0334438.ref029","unstructured":"Wickham H, Fran\u00e7ois R, Henry L, M\u00fcller K, Vaughan D. dplyr: A Grammar of Data Manipulation [Internet]. 2023. Available from: https:\/\/CRAN.R-project.org\/package=dplyr"},{"key":"pone.0334438.ref030","author":"H Wickham","year":"2016"},{"key":"pone.0334438.ref031","unstructured":"Huntington-Klein N. vtable: Variable Table for Variable Documentation [Internet]. 2023. Available from: https:\/\/CRAN.R-project.org\/package=vtable"},{"issue":"3","key":"pone.0334438.ref032","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11908-017-0568-7","article-title":"Herpes Simplex Encephalitis: an Update","volume":"19","author":"JW Gnann","year":"2017","journal-title":"Curr Infect Dis Rep"},{"issue":"8","key":"pone.0334438.ref033","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1007\/s004150070134","article-title":"Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction","volume":"247","author":"M Studahl","year":"2000","journal-title":"J Neurol"},{"issue":"10","key":"pone.0334438.ref034","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1111\/ene.15978","article-title":"Serum and cerebrospinal fluid brain damage markers neurofilament light and glial fibrillary acidic protein correlate with tick-borne encephalitis disease severity-a multicentre study on Lithuanian and Swedish patients","volume":"30","author":"M Veje","year":"2023","journal-title":"Eur J Neurol"},{"issue":"1","key":"pone.0334438.ref035","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s13643-025-02797-0","article-title":"Unveiling the clinical spectrum of herpes simplex virus CNS infections in adults: a systematic review","volume":"14","author":"P Grzonka","year":"2025","journal-title":"Syst Rev"},{"issue":"4","key":"pone.0334438.ref036","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000200255","article-title":"Racial and Ethnic Disparities in the Incidence of Anti-NMDA Receptor Encephalitis","volume":"11","author":"S Alsalek","year":"2024","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"pone.0334438.ref037","unstructured":"European Centre for Disease Prevention and Control. Tick-borne encephalitis Annual Epidemiological Report 2022. 2022; Available from: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/tick-borne-encephalitis-annual-epidemiological-report-2022"},{"issue":"4","key":"pone.0334438.ref038","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.bpsgos.2022.10.007","article-title":"Antineuronal Autoantibodies in the Cerebrospinal Fluid and Serum From 106 Patients With Recent-Onset Depression Compared With 106 Individually Matched Healthy Control Subjects","volume":"3","author":"NV S\u00f8rensen","year":"2022","journal-title":"Biol Psychiatry Glob Open Sci"},{"issue":"1","key":"pone.0334438.ref039","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/s41398-021-01701-3","article-title":"Screening for pathogenic neuronal autoantibodies in serum and CSF of patients with first-episode psychosis","volume":"11","author":"J Theorell","year":"2021","journal-title":"Transl Psychiatry"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0334438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T17:22:02Z","timestamp":1760376122000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0334438"}},"subtitle":[],"editor":[{"given":"Karlo","family":"Toljan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,13]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0334438","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,13]]}}}