이상건 (서울대학교 의과대학)

한빛사논문

조회754

서울대학교 의과대학

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Ann. Neurol., First published 7 January 2021 | https://doi.org/10.1002/ana.26017 CaVα2δ Autoimmune Encephalitis: A Novel Antibody and its Characteristics

Soon-Tae Lee MD PhD,^1,†,* Byoung Ju Lee PhD,^2,†Ji-Yeon Bae MS,^1,†$Young Sook Kim MD,¹Do-Hyun Han PhD,^3,4 Hyun-Sook Shin MS,³ Soyun Kim MS,¹ Dong-Kyu Park BS,¹ Sang Won Seo MD PhD,⁵ Kon Chu MD PhD,¹ Sang Kun Lee MD PhD,^1,* Won-Kyung Ho MD PhD^2,6,*

¹Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
²Department of Physiology and Neuroscience Research Center, Seoul National University College of Medicine, Seoul, South Korea
³Proteomics Core Facility, Seoul National University Hospital, Seoul, South Korea
⁴Proteomics & Biomarker Laboratory Departments of Biomedical Engineering & Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea
⁵Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
⁶Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.

^†These authors share the first authorship.

^*Corresponding author

Abstract

Objective
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.

Method
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.

Results
Two patients had a novel antibody against Ca_Vα2δ (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 Ca_Vα2δ‐overexpressing cell line. Knockdown of the Ca_Vα2δ 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.

Interpretation
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.

논문정보

형식Research article
게재일2021년 01월 (BRIC 등록일 2021-01-12)
연구진국내 연구진
분야 의약학 > 신경의학

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