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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,31]]},"abstract":"<jats:p>\n                    The immunopathogenesis of autoimmune neurological syndromes (AINS) with antibodies against the 65 kDa isoform of glutamic acid decarboxylase (anti-GAD65 AINS) remains poorly understood. To elucidate underlying disease mechanisms and identify relevant cell populations, we performed single-cell RNA and immune repertoire sequencing of cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) of eight anti-GAD65 AINS individuals compared to eight noninflammatory controls. In addition, PBMCs from 19 anti-GAD65 AINS individuals and 20 healthy controls were analyzed by multidimensional flow cytometry, and brain tissue specimens from four anti-GAD65 AINS individuals were examined histologically. We detected higher frequencies of stem cell\u2013like memory T cells (TSCM) within the PBMCs and a marked enrichment and clonal expansion of activated CD4\n                    <jats:sup>+<\/jats:sup>\n                    TSCM in the CSF of anti-GAD65 AINS individuals. Expanded T cells exhibited increased expression of proinflammatory genes. Histological analyses confirmed intraparenchymal CD8\n                    <jats:sup>+<\/jats:sup>\n                    TSCM in three of four anti-GAD65 AINS individuals and rare meningeal\/intraparenchymal CD4\n                    <jats:sup>+<\/jats:sup>\n                    TSCM in one person. Although CSF B cell receptors (BCRs) displayed little to no clonal expansion, recombinant expression of 40 CSF BCRs revealed that 25% were GAD65-reactive with increased somatic hypermutations compared to non-GAD65-reactive BCRs. These findings further support the concept of an antigen-specific intrathecal immune response. In summary, we characterize the immune landscape of anti-GAD65 AINS at single-cell resolution and identify clonally expanded TSCM with cytotoxic properties as a hallmark of this disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2514753123","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:07:16Z","timestamp":1774462036000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Immune cell profiling reveals expanded stem cell\u2013like memory T cells in anti-GAD65-associated neurological syndromes"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-402X","authenticated-orcid":false,"given":"Sumanta","family":"Barman","sequence":"first","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University","place":["D\u00fcsseldorf, 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