{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:35:07Z","timestamp":1793118907003,"version":"4.5.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS098229"],"award-info":[{"award-number":["NS098229"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS102417"],"award-info":[{"award-number":["NS102417"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pediatric and adult autoimmune encephalitis (AE) are often associated with Abs to the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor (NMDAR). Very little is known regarding the cerebrospinal fluid humoral immune profile and Ab genetics associated with pediatric anti\u2013NMDAR-AE. Using a combination of cellular, molecular, and immunogenetics tools, we collected cerebrospinal fluid from pediatric subjects and generated 1) flow cytometry data to calculate the frequency of B cell subtypes in the cerebrospinal fluid of pediatric subjects with anti\u2013NMDAR-AE and controls, 2) a panel of recombinant human Abs from a pediatric case of anti\u2013NMDAR-AE that was refractory to treatment, and 3) a detailed analysis of the Ab genes that bound the NR1 subunit of the NMDAR. Ag-experienced B cells including memory cells, plasmablasts, and Ab-secreting cells were expanded in the pediatric anti\u2013NMDAR-AE cohort, but not in the controls. These Ag-experienced B cells in the cerebrospinal fluid of a pediatric case of NMDAR-AE that was refractory to treatment had expanded use of variable H chain family 2 (VH2) genes with high somatic hypermutation that all bound to the NR1 subunit of the NMDAR. A CDR3 motif was identified in this refractory case that likely drove early stage activation and expansion of naive B cells to Ab-secreting cells, facilitating autoimmunity associated with pediatric anti\u2013NMDAR-AE through the production of Abs that bind NR1. These features of humoral immune responses in the cerebrospinal fluid of pediatric anti\u2013NMDAR-AE patients may be relevant for clinical diagnosis and treatment.<\/jats:p>","DOI":"10.4049\/jimmunol.2300156","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T13:16:19Z","timestamp":1694783779000},"page":"1332-1339","source":"Crossref","is-referenced-by-count":3,"title":["VH2+ Antigen-Experienced B Cells in the Cerebrospinal Fluid Are Expanded and Enriched in Pediatric Anti-NMDA Receptor Encephalitis"],"prefix":"10.1093","volume":"211","author":[{"given":"Nancy","family":"Monson","sequence":"first","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"},{"name":"Department of Immunology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6949-995X","authenticated-orcid":false,"given":"Chad","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Plumb","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0164-7412","authenticated-orcid":false,"given":"Alyssa","family":"Guzman","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Key","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley","family":"Speed","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Civitan International Research Center, University of Alabama Marnix E. Heersink School of Medicine , Birmingham, AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0964-975X","authenticated-orcid":false,"given":"Sushobhna","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Cowell","sequence":"additional","affiliation":[{"name":"Department of Population and Data Sciences, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9889-1221","authenticated-orcid":false,"given":"Scott","family":"Christley","sequence":"additional","affiliation":[{"name":"Department of Population and Data Sciences, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7799-8495","authenticated-orcid":false,"given":"Steve","family":"Vernino","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Blackburn","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2091-8201","authenticated-orcid":false,"given":"Benjamin","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, UT Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"2025020406170923500_r1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3988\/jcn.2022.18.4.373","article-title":"Autoantibody encephalitis: presentation, diagnosis, and management","volume":"18","author":"Lancaster","year":"2022","journal-title":"J. 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