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GAD-Abs are not considered directly pathogenic and immunotherapy guidelines are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We undertook a single-center retrospective service evaluation of GAD-Abs, documenting clinical features, immunotherapy responses, and outcomes of 335 patients with positive GAD-Abs measured by indirect ELISA between 2012 and 2020. The serum:CSF ratio of GAD-Ab values was used as a surrogate for intrathecal synthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      168 (50%) patients had diagnosed neurological disorders (GAD-ND). Ninety-six had neurological disorders often or sometimes associated with GAD-Abs, i.e., stiff person syndrome spectrum disorders (SPS-SD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200926), cerebellar ataxia (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200921), epilepsy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200919), encephalitis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918), or any combination of these (\u201cmixed\u201d,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912). Seventy-two had other neurological disorders (ONDs) not typically associated with GAD-Abs.\n                    <\/jats:p>\n                    <jats:p>We defined a cut-off of 10,000\u00a0IU\/mL a priori and a posteriori for GAD-Ab associated NDs, but identified values\u2009&gt;\u200910,000\u00a0IU\/mL in 21% and 11% of patients with ONDs or diabetes respectively, and\u2009&lt;\u200910,000\u00a0IU\/mL in 39% patients with classical GAD-Ab syndromes, indicating low assay specificity and sensitivity.<\/jats:p>\n                    <jats:p>\n                      Low serum: CSF GAD-Ab ratios were consistent with intrathecal synthesis in 12\/19 tested; 25\/54 patients had oligoclonal bands. 30\/50 patients given adequate immunotherapies had partial (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200917) or good (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913) responses, particularly those with SPS-SD or limbic encephalitis. Within the limitations of small subgroups and routine laboratory titrations, patients with GAD-Ab values\u2009&gt;\u200910,000\u00a0IU\/mL, intrathecal synthesis of GAD-Abs, or oligoclonal bands, were not more likely to improve with immunotherapies than those with GAD-Ab values\u2009&lt;\u200910,000\u00a0IU\/mL and a non-inflammatory CSF. Rather, treatment response correlated with disease group, principally SPS-SD and encephalitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest caution in over-interpreting GAD-Abs values. Better biomarkers for identifying patients with immunotherapy responsive GAD-Ab disease are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-025-12926-3","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T06:26:36Z","timestamp":1740205596000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["GAD antibodies in neurological disease: a critical evaluation of the utility and treatment implications of GAD antibodies in clinical practice"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9932-0228","authenticated-orcid":false,"given":"Rachel L.","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Thomas-Black","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Garcia-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zofia","family":"Fleszar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Zandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Church","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Giunti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Lunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"issue":"5","key":"12926_CR1","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1002\/j.1460-2075.1991.tb08069.x","volume":"10","author":"A Reetz","year":"1991","unstructured":"Reetz A, Solimena M, Matteoli M, Folli F, Takei K, De Camilli P (1991) GABA and pancreatic beta-cells: colocalization of glutamic acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion. 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MH has received consulting fees from Accenture Consulting.\u00a0PG\u00a0has received grants and honoraria for advisory board from Vico Therapeutics, honoraria for advisory board from Triplet Therapeutics, grants and personal fees from Reata Pharmaceutical, grants from Wave. AV and the University of Oxford receive royalties for LGI1 and CASPR2 antibodies. AV has received lecture fees from Alexion, UCB and Johnson&Johnson.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"222"}}