title: Proteomic analysis of human brain identifies alpha-enolase as a novel autoantigen in Hashimoto's encephalopathy.
abstract: 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, alpha-enolase, harboring several modifications. Specific high reactivities against human alpha-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 alpha-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-alpha-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.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ochi
authors.forename: Izumi
authors.initials: I
authors.lastname: Horiuchi
authors.forename: Norie
authors.initials: N
authors.lastname: Araki
authors.forename: Tosifusa
authors.initials: T
authors.lastname: Toda
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Araki
authors.forename: Kaori
authors.initials: K
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murai
authors.forename: Manabu
authors.initials: M
authors.lastname: Osoegawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Ken
authors.initials: K
authors.lastname: Okamura
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ogino
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kira
mesh_terms: D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000235:genetics*; D001921:Brain / Q000201:enzymology* / Q000276:immunology*; D001927:Brain Diseases / Q000201:enzymology* / Q000276:immunology*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D010751:Phosphopyruvate Hydratase / Q000235:genetics* / Q000276:immunology*; D020543:Proteome; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013967:Thyroiditis, Autoimmune / Q000201:enzymology* / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D020543:Proteome; D011994:Recombinant Proteins; D010751:Phosphopyruvate Hydratase