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Various techniques, including immunoblotting, immunoprecipitation, mass spectrometry, immunohistochemistry, and in\u00a0vitro assays assessing neuronal autoantibody uptake, neuronal viability, pyruvate dehydrogenase (PDH) enzyme activity, and mitochondrial DNA levels in biofluids were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mass spectrometry detected all three subunits of the intramitochondrial PDHc\u2014pyruvate dehydrogenase, dihydrolipoyl acetyltransferase, and dihydrolipoyl dehydrogenase\u2014as targets of antibodies present in serum samples from three index patients suspicious for AIE with psychiatric symptoms or seizures. The presence of the anti\u2010PDHc autoantibodies was confirmed by immunoblotting in 12 of 387 patients. Exposure of cultured primary neurons to commercial anti\u2010PDH antibodies resulted in neuronal uptake and loss of neuronal viability. Patient\u2010derived autoantibodies also impaired PDH enzyme activity in\u00a0vitro. Additionally, cell\u2010free mitochondrial DNA fragment levels were elevated in the serum and cerebrospinal fluid of PDH\u2010positive patients compared to controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Anti\u2010PDH autoantibodies were detected in patients suspicious for AIE with seizures and\/or psychiatric symptoms as core manifestation in the absence of known antineuronal autoantibodies. These autoantibodies bind neuronal structures and reduce PDH enzyme activity under experimental conditions, supporting mechanistic plausibility of a functional role in disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70282","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:54:32Z","timestamp":1778770472000},"page":"4078-4094","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pyruvate dehydrogenase autoantibodies in autoantibody\u2010negative patients with seizures are associated with reduced pyruvate dehydrogenase activity"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2401-0013","authenticated-orcid":false,"given":"Annika","family":"Breuer","sequence":"first","affiliation":[{"name":"Department of Epileptology University Hospital Bonn, University of Bonn  Bonn 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