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The emergence of post-HSE autoimmune encephalitis reveals a new immunological paradigm in autoantibody-mediated disease. A reductionist evaluation of the immunobiological mechanisms in HSE is crucial to dissect the origins of post-viral autoimmunity and supply rational approaches to the selection of immunotherapeutics.<\/jats:p>\n                  <jats:p>Herein, we review the latest evidence behind the phenotypic progression and underlying immunobiology of HSE including the cytokine\/chemokine environment, the role of pathogen-recognition receptors, T- and B-cell immunity and relevant inborn errors of immunity. Second, we provide a contemporary review of published patients with post-HSE autoimmune encephalitis from a combined cohort of 110 patients. Third, we integrate novel mechanisms of autoimmunization in deep cervical lymph nodes to explore hypotheses around post-HSE autoimmune encephalitis and challenge these against mechanisms of molecular mimicry and others. Finally, we explore translational concepts where neuroglial surface autoantibodies have been observed with other neuroinfectious diseases and those that generate brain damage including traumatic brain injury, ischaemic stroke and neurodegenerative disease.<\/jats:p>\n                  <jats:p>Overall, the clinical and immunological landscape of HSE is an important and evolving field, from which precision immunotherapeutics could soon emerge.<\/jats:p>","DOI":"10.1093\/brain\/awad419","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T21:17:14Z","timestamp":1702502234000},"page":"1130-1148","source":"Crossref","is-referenced-by-count":66,"title":["The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9657-5815","authenticated-orcid":false,"given":"Jonathan","family":"Cleaver","sequence":"first","affiliation":[{"name":"Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford, OX3 9DU , UK"},{"name":"Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals , Oxford, OX3 9DU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Jeffery","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Oxford University Hospitals NHS Foundation Trust , Oxford, OX3 9DU , UK"},{"name":"Radcliffe Department of Medicine, University of Oxford , Oxford, OX3 9DU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-9161","authenticated-orcid":false,"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford , Oxford, OX1 3SY , UK"},{"name":"Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford , Oxford, OX3 9DU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Lim","sequence":"additional","affiliation":[{"name":"Children\u2019s Neurosciences, Evelina London Children\u2019s Hospital at Guy\u2019s and St Thomas\u2019 NHS Foundation Trust , London, SE1 7EH , UK"},{"name":"Department Women and Children\u2019s Health, School of Life Course Sciences, King\u2019s College London , London, WC2R 2LS , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lahiru","family":"Handunnetthi","sequence":"additional","affiliation":[{"name":"Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford, OX3 9DU , UK"},{"name":"Wellcome Centre for Human Genetics, University of Oxford , Oxford, OX3 7BN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7667-9748","authenticated-orcid":false,"given":"Sarosh R","family":"Irani","sequence":"additional","affiliation":[{"name":"Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford, OX3 9DU , UK"},{"name":"Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals , Oxford, OX3 9DU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-6346","authenticated-orcid":false,"given":"Adam","family":"Handel","sequence":"additional","affiliation":[{"name":"Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford, OX3 9DU , UK"},{"name":"Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals , Oxford, OX3 9DU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"2024040418425452700_awad419-B1","doi-asserted-by":"crossref","first-page":"e104169","DOI":"10.1371\/journal.pone.0104169","article-title":"Encephalitis hospitalization rates and inpatient mortality in the United States, 2000\u20132010","volume":"9","author":"George","year":"2014","journal-title":"PLoS One"},{"key":"2024040418425452700_awad419-B2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.medmal.2017.02.003","article-title":"Epidemiology of infectious encephalitis causes in 2016","volume":"47","author":"Boucher","year":"2017","journal-title":"Med Mal Infect"},{"key":"2024040418425452700_awad419-B3","doi-asserted-by":"crossref","first-page":"766","DOI":"10.2471\/BLT.10.085233","article-title":"Estimated global incidence of Japanese encephalitis: A systematic 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