Expression of <i>N</i>-Methyl-D-Aspartate Receptor Subunits in the Bovine Ovum: Ova as a Potential Source of Autoantigens Causing Anti-NMDAR Encephalitis
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- Tachibana Naoko
- Department of Neurology, Okaya City Hospital
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- Kinoshita Michiaki
- Department of Medicine (Neurology & Rheumatology), Shinshu University School of Medicine
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- Kametani Fuyuki
- Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science
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- Tanaka Keiko
- Department of Life Science, Medical Research Institute, Kanazawa Medical University Department of Neurology, Kanazawa Medical University
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- Une Yumi
- Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University
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- Komatsu Yotaro
- Nagano Public Animal Industry Station
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- Kobayashi Yukihiro
- Department of Laboratory Medicine, Shinshu University School of Medicine
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- Ikeda Shu-ichi
- Department of Medicine (Neurology & Rheumatology), Shinshu University School of Medicine
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抄録
Autoimmune synaptic encephalitis is characterized by the presence of autoantibodies against synaptic constituent receptors and manifests as neurological and psychiatric disorders. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is such an autoimmune disorder that predominantly affects young women. It is associated with antibodies against the extracellular region of the NR1 subunit of postsynaptic NMDAR. Each NMDAR functions as a heterotetrameric complex that is composed of four subunits, including NR1 and NR2A, NR2B, or NR2C. Importantly, ovarian teratoma is a typical complication of anti-NMDAR encephalitis in female patients and may contain antigenic neural tissue; however, antigenic sites remain unknown in female patients without ovarian teratoma. The purpose of this study was to investigate the expression of NMDARs in the ovum. We detected NR1 and NR2B immunoreactivity in protein fractions extracted from the bovine ovary and ova by SDS-polyacrylamide gel electrophoresis and immunoblotting analysis. Immunoprecipitates digested with trypsin were analyzed by reverse phase liquid chromatography coupled to tandem mass spectrometry. We obtained the following five peptides: SPFGRFK and KNLQDR, which are consistent with partial sequences of human NR1, and GVEDALVSLK, QPTVAGAPK, and NEVMSSK, which correspond to those of NR2A, NR2B and NR2C, respectively. Immunocytochemical analysis revealed that the bovine ovum was stained with the immunoglobulin G purified from the serum of a patient with anti-NMDAR encephalitis. Taken together, we propose that the normal ovum expresses NMDARs that have strong affinity for the disease-specific IgG. The presence of NMDARs in ova may help explain why young females without ovarian teratomas are also affected by anti-NMDAR encephalitis.
収録刊行物
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 235 (3), 223-231, 2015
東北ジャーナル刊行会