Ca V α2δ Autoimmune Encephalitis: A Novel Antibody and its Characteristics

Autor: Young Sook Kim, Kon Chu, Sang Kun Lee, Dohyun Han, Sang Won Seo, Soon-Tae Lee, Won-Kyung Ho, Hyun Sook Shin, Dong Kyu Park, Soyun Kim, Byoung Joo Lee, Ji Yeon Bae
Rok vydání: 2021
Předmět:
Zdroj: Annals of Neurology. 89:740-752
ISSN: 1531-8249
0364-5134
DOI: 10.1002/ana.26017
Popis: OBJECTIVE 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. METHOD 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-spectrometry analysis, an antigen-binding assay on an antigen-overexpressing cell line, and an electrophysiological assay with cultured hippocampal neurons. RESULTS Two patients had a novel antibody against CaV α2δ (voltage-gated calcium channel alpha-2/delta subunit). The patient samples stained neuropils of the hippocampus, basal ganglia, and cortex in rat brain sections and bound to a CaV α2δ-overexpressing cell line. Knockdown of CaV α2δ 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. INTERPRETATION Here, we discovered a novel autoimmune encephalitis associated with anti-CaV α2δ antibody. Further analysis of the antibody in autoimmune encephalitis might promote early diagnosis and treatment. ANN NEUROL 2021;89:740-752.
Databáze: OpenAIRE
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