Proteomic analysis of human brain identifies α‐enolase as a novel autoantigen in Hashimoto's encephalopathy

FEBS Letters

Araki, Tomohiro⁷  Murai, Hiroyuki³  Osoegawa, Manabu³  Toda, Tosifusa⁵  Yamada, Takeshi¹  Araki, Norie⁴  Ochi, Hirofumi³  Ogino, Tomoaki²  Horiuchi, Izumi³  Sato, Kaori⁸  Saya, Hideyuki⁴  Yamashita, Hirohumi⁶  Mizumoto, Kiyohisa²  Okamura, Ken⁸  Kira, Jun-ichi³ 

[1] Department of Neurology, Aso Iizuka Hospital, Iizuka 820-8505, Japan;Department of Biochemistry, School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan;Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;Department of Tumor Genetics and Biology, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan;Proteomics Collaboration Center, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan;Department of Neurology and Brain Pathology, Graduate School of Medicine, Kyoto University, Kyoto 660-8501, Japan;Department of Bioscience, School of Agriculture, Kyushu Tokai University, Kumamoto 869-1404, Japan;Second Department of Internal Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

关键词: α-enolase;    Autoantigen;    Proteomics;    Two-dimensional electrophoresis;    Brain;    HE;    Hashimoto's encephalopathy;    HT;    Hashimoto's thyroiditis;    2-DE;    two-dimensional gel electrophoresis;    MALDI-TOF;    matrix-assisted laser desorption ionization time-of-flight;    CNS;    central nervous system;    BPB;    bromophenol blue;    IPG;    immobilized pH gradient;    PVDF;    polyvinylidene difluoride;    CBB;    Coomassie Brilliant Blue;    OND;    other neurological disorder;    HC;    healthy subject;   

DOI  :  10.1016/S0014-5793(02)03307-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Hashimoto's encephalopathy (HE) is a rare autoimmune disease associated with Hashimoto's thyroiditis (HT). To identify the HE-related autoantigens, we developed a human brain proteome map using two-dimensional electrophoresis and applied it to the immuno-screening of brain proteins that react with autoantibodies in HE patients. After sequential MALDI-TOF-MASS analysis, immuno-positive spots of 48 kDa (pI 7.3–7.8) detected from HE patient sera were identified as a novel autoimmuno-antigen, α-enolase, harboring several modifications. Specific high reactivities against human α-enolase were significant in HE patients with excellent corticosteroid sensitivity, whereas the patients with fair or poor sensitivity to the corticosteroid treatment showed less reactivities than cut-off level. Although a few HT patients showed faint reactions to α-enolase, 95% of HT patients, patients with other neurological disorders, and healthy subjects tested were all negative. These results suggest that the detection of anti-α-enolase antibody is useful for defining HE-related pathology, and this proteomic strategy is a powerful method for identifying autoantigens of various central nervous system diseases with unknown autoimmune etiologies.

【 授权许可】

Unknown