Discovering novel antibody enables diagnosis and early treatment of the autoimmune encephalitis. We discovered a novel antibody targeting a synaptic receptor and characterized the pathogenic mechanism.
We screened for unknown antibodies in serum and CSF samples from autoimmune encephalitis patients. Samples with reactivity to rat brain sections and no reactivity to conventional antibody tests underwent further process for antibody discovery, using immunoprecipitation to primary neuronal cells, mass‐spectrometry analysis, antigen‐binding assay on antigen‐overexpressed cell line, and electrophysiology assay with cultured hippocampal neurons.
Two patients had a novel antibody against CaVα2δ (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 CaVα2δ‐overexpressing cell line. Knockdown of the CaVα2δ expression in cultured neurons turned off the immunoreactivity of the patients' antibody 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.
Here, we found a novel autoimmune encephalitis associated with anti‐CaVα2δ antibody. Further analysis of the antibody in autoimmune encephalitis might promote the early diagnosis and treatment.