{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:03:26Z","timestamp":1776351806908,"version":"3.51.2"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Autoimmune neurological syndromes (AINS) associated with anti-GAD65 antibodies encompass a spectrum of disorders, including limbic encephalitis (LE), stiff-person syndrome (SPS), and cerebellar ataxia (CA). Despite the universal presence of anti-GAD65 antibodies across these syndromes, patients exhibit remarkable clinical phenotypic diversity. Exploring the overall B-cell receptor (BCR) profile of patients with anti-GAD65 AINS may provide clues to the molecular pathological mechanisms underlying this phenotypic diversity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed high-throughput B-cell receptor (BCR) heavy-chain sequencing (Illumina NovaSeq 6000) on peripheral blood samples from 9 anti-GAD65 AINS patients (7 LE, 1 SPS, 1 CA\/SPS overlapping) and 11 healthy controls (HC). Analysis encompasses clonotype profiling, somatic hypermutation (SHM) rates, CDR3 physicochemical characterization, repertoire diversity, and machine learning-based VDJ feature identification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Anti-GAD65 LE showed significantly reduced repertoire diversity versus HC (Chao1:\n                      <jats:italic>p<\/jats:italic>\n                      -adjusted = 0.0023; Hill:\n                      <jats:italic>p<\/jats:italic>\n                      -adjusted = 3.7 \u00d7 10\n                      <jats:sup>\u2013<\/jats:sup>\n                      \u2075), lower SHM rates (3.54% vs. 4.73%), and enrichment of hyperexpanded clones. Distinct IGHV\/IGHJ usage was identified, notably decreased IGHV1-2 and IGHV1-46 with elevated IGHV3-7. A random forest classifier built on characteristic VDJ clonotypes achieved near-perfect diagnostic performance (AUC &amp;gt; 0.99). Cross-patient shared clonal clusters further highlighted disease-associated BCR convergence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BCR repertoire heterogeneity across anti-GAD65 AINS subtypes illuminates the immunological underpinnings of phenotypic diversity. The identified VDJ signatures and common clonotypes represent candidate biomarkers for precise diagnosis and rational targets for BCR-lineage-directed immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1668617","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:17:21Z","timestamp":1776349041000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["B-cell immune repertoire analysis of autoimmune neurological syndromes with anti-GAD65 antibodies"],"prefix":"10.3389","volume":"16","author":[{"given":"Tianya","family":"Dong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences","place":["Beijing, China"]},{"name":"Department of Psychology, University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haitao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinwei","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences","place":["Beijing, China"]},{"name":"Department of Psychology, University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongzhi","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences","place":["Beijing, China"]},{"name":"Department of Psychology, University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1007\/s13311-022-01188-w","article-title":"Stiff-person syndrome and GAD antibody-spectrum disorders: 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