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This study aimed to investigate the clinical heterogeneity, immunological characteristics, neuropathological features, and therapeutic outcomes in patients with anti-GAD65 AE. A retrospective study was performed in six patients with anti-GAD65 AE diagnosed at Guangdong Provincial People\u2019s Hospital. Collected data included demographic, clinical manifestations, cerebrospinal fluid (CSF) profiles, neuroimaging findings, antibody titers, immunotherapy regimens, and histopathology. Initial presentations included epilepsy (50%), hyperthyroidism (33%), and stiff-person syndrome (17%). Concurrent autoimmune diseases (type 1 diabetes, autoimmune thyroiditis, and polyendocrine syndrome) were present in half of the patients. All patients exhibited elevated anti-GAD65 antibody titers in serum and CSF. CSF analysis revealed lymphocytic pleocytosis in one patient and oligoclonal bands in four tested cases. Acute immunotherapy involving corticosteroids and intravenous immunoglobulin achieved seizure control in 83%. Maintenance therapy with mycophenolate mofetil or biologics (e.g., ofatumumab, telitacicept) elicited heterogeneous serological responses, including antibody titer rebound despite clinical stability. Notably, Case 6 represented the first reported case worldwide of AE with triple positivity (anti-GAD65, anti-GABA\n                    <jats:sub>A<\/jats:sub>\n                    R\u03b11, and anti-GQ1b IgG antibodies), presenting with rapidly progressive cognitive impairment, extensive parenchymal lesions, and extremely high anti-GAD65 titers, yet exhibited significant improvement post-immunotherapy. Histopathology revealed CD3\u207a\/CD8\u207a T-cell infiltrates in perivascular, meningeal, and parenchymal regions, accompanied by aggregates of CD20\u207a B cells, CD38\u207a plasma cells, GrB\u207a non-T cells (e.g., NK cells), and activated CD68\u207a macrophages\/microglia. Anti-GAD65 AE exhibits marked clinical and immunological heterogeneity, involving both humoral and T-cell-mediated pathogenic mechanisms. Coexisting antibodies may exacerbate neuronal injury through mechanisms such as antigen unmasking and antibody-dependent cellular cytotoxicity. Persistent antibody elevation and subclinical immune activity underscore the necessity of integrating multimodal biomarkers and developing personalized treatment strategies.\n                  <\/jats:p>","DOI":"10.1177\/17562864261456519","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T03:43:52Z","timestamp":1781063032000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical heterogeneity and immunotherapy outcomes in anti-GAD65 antibody-associated autoimmune encephalitis: a retrospective study"],"prefix":"10.1177","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0451-9091","authenticated-orcid":false,"given":"Yihui","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengyun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihuan","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixian","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3492-4669","authenticated-orcid":false,"given":"Yuhu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan 2nd Road, Guangzhou, Guangdong Province 510080, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiehao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan 2nd Road, Guangzhou, Guangdong Province 510080, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2020.577289"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2020.106082"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13020369"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.11.7755"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1274672"},{"key":"e_1_3_4_7_2","article-title":"Co-occurrence of anti-GAD65 syndrome, type 1 diabetes mellitus, and focal seizures with impaired awareness","volume":"15","author":"Bach K","year":"2023","unstructured":"Bach K, Ananth S, Thind I, et al. 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