{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:58:38Z","timestamp":1773403118356,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Discovery of a novel antibody would enable diagnosis and early treatment of autoimmune encephalitis. The aim was to discover a novel antibody targeting a synaptic receptor and characterize the pathogenic mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We screened for unknown antibodies in serum and cerebrospinal fluid samples from autoimmune encephalitis patients. Samples with reactivity to rat brain sections and no reactivity to conventional antibody tests underwent further processing for antibody discovery, using immunoprecipitation to primary neuronal cells, mass\u2010spectrometry analysis, an antigen\u2010binding assay on an antigen\u2010overexpressing cell line, and an electrophysiological assay with cultured hippocampal neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two patients had a novel antibody against Ca<jats:sub>V<\/jats:sub>\u03b12\u03b4 (voltage\u2010gated calcium channel alpha\u20102\/delta subunit). The patient samples stained neuropils of the hippocampus, basal ganglia, and cortex in rat brain sections and bound to a Ca<jats:sub>V<\/jats:sub>\u03b12\u03b4\u2010overexpressing cell line. Knockdown of Ca<jats:sub>V<\/jats:sub>\u03b12\u03b4 expression in cultured neurons turned off the immunoreactivity of the antibody from the patients to the neurons. The patients were associated with preceding meningitis or neuroendocrine carcinoma and responded to immunotherapy. In cultured neurons, the antibody reduced neurotransmitter release from presynaptic nerve terminals by interfering with tight coupling of calcium channels and exocytosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Here, we discovered a novel autoimmune encephalitis associated with anti\u2010Ca<jats:sub>V<\/jats:sub>\u03b12\u03b4 antibody. Further analysis of the antibody in autoimmune encephalitis might promote early diagnosis and treatment. 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