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However, the drivers of the antibody-secreting cells and involvement of T cells remain unresolved. We performed single-cell RNA sequencing of fresh CSF and parallel blood samples of 15 patients with LGI1-AIE (n = 9) and CASPR2-AIE (n = 6) compared with control patients [multiple sclerosis (n = 15) and idiopathic intracranial hypertension (n = 18)]. We validated our observations in independent cohorts using flow cytometry of CSF and blood. We confirmed autoantibody specificity using recombinant human monoclonal antibodies.<\/jats:p>\n                  <jats:p>In comparison to idiopathic intracranial hypertension and multiple sclerosis controls, we observed clonal CSF-specific antibody-secreting cell expansion in LGI1\/CASPR2-AIE despite mostly normal CSF findings. Antibody-secreting cells were dominantly plasmablasts and transcribed IgG4 and IgG1\/2 heavy chains. Expanded clones showed signs of affinity maturation and bound the respective neuronal autoantigen. Within CD4 and CD8 T-cell clusters, CD4 and CD8 central memory T cells were activated, clonally restricted and expanded. T-cell clones were often shared between CSF and blood. We also observed a shift of natural killer cells and loss of mucosa-associated invariant T (MAIT) cells in the CSF of LGI1-AIE and the blood of LGI1- and CASPR2-AIE compared with idiopathic intracranial hypertension and multiple sclerosis controls. MAIT-like T cells were detected in autopsied brains of LGI1- and CASPR2-AIE patients, and mice lacking MAIT cells displayed an increased antibody seroconversion and higher titres following active LGI1\/CASPR2 immunization.<\/jats:p>\n                  <jats:p>Our data: (i) confirm the intrathecal antigen-specific plasma cell expansion in LGI1- and CASPR2-AIE in a large cohort of untreated AIE patients; (ii) suggest that activated and expanded central memory CD4 and CD8 T cells in the CSF participate in disease pathogenesis; and (iii) implicate invariant T-cell receptor-expressing lymphocytes in the brain, CSF and blood in disease pathogenesis.<\/jats:p>","DOI":"10.1093\/brain\/awaf096","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T16:24:44Z","timestamp":1741883084000},"page":"3170-3183","source":"Crossref","is-referenced-by-count":20,"title":["Activated \u03b1\u03b2 T and reduced mucosa-associated invariant T cells in LGI1- and CASPR2-encephalitis"],"prefix":"10.1093","volume":"148","author":[{"given":"Daniela","family":"Esser","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel\/L\u00fcbeck , Kiel 24103, Schleswig-Holstein ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"M\u00fcller-Miny","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital M\u00fcnster , M\u00fcnster 48143, North Rhine-Westphalia ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Heming","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital M\u00fcnster , M\u00fcnster 48143, North Rhine-Westphalia ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Paunovic","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus MC University Medical Center , Rotterdam 3000 DR ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6654-994X","authenticated-orcid":false,"given":"Martijn","family":"van Duijn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus MC University Medical Center , Rotterdam 3000 DR ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligia","family":"Abrante Cabrera","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel\/L\u00fcbeck , Kiel 24103, Schleswig-Holstein ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina M","family":"Mair","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Strippel","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital M\u00fcnster , M\u00fcnster 48143, North Rhine-Westphalia ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8901-5572","authenticated-orcid":false,"given":"Saskia","family":"R\u00e4uber","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital M\u00fcnster , M\u00fcnster 48143, North Rhine-Westphalia ,","place":["Germany"]},{"name":"Department of Neurology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf , D\u00fcsseldorf 40225, North Rhine-Westphalia ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina","family":"Dargvainiene","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel\/L\u00fcbeck , Kiel 24103, Schleswig-Holstein ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2500-6893","authenticated-orcid":false,"given":"Stjepana","family":"Kovac","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital M\u00fcnster , M\u00fcnster 48143, North Rhine-Westphalia ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-9189","authenticated-orcid":false,"given":"Catharina C","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital M\u00fcnster , M\u00fcnster 48143, North Rhine-Westphalia ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Fransen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam UMC , Amsterdam 1098XH ,","place":["The Netherlands"]},{"name":"Department of Pathology, UMC Utrecht , Utrecht 2521CB ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"van Steenhoven","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus MC University Medical Center , Rotterdam 3000 DR ,","place":["The 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,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1033-3840","authenticated-orcid":false,"given":"Maarten J","family":"Titulaer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus MC University Medical Center , Rotterdam 3000 DR ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8972-515X","authenticated-orcid":false,"given":"Frank","family":"Leypoldt","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, University Hospital Schleswig-Holstein Kiel\/L\u00fcbeck , Kiel 24103, Schleswig-Holstein ,","place":["Germany"]},{"name":"Department of Neurology, University Hospital Schleswig-Holstein , Kiel 24103, Schleswig-Holstein ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4341-4719","authenticated-orcid":false,"given":"Gerd","family":"Meyer zu H\u00f6rste","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital M\u00fcnster , M\u00fcnster 48143, North Rhine-Westphalia ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"in cooperation with the EMC-AIE Study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juna M","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariska M P","family":"Nagtzaam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne 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