Proteomic analysis of human brain identifies alpha-enolase as a novel autoantigen in Hashimoto's encephalopathy.
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.
Ochi
Hirofumi
H
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Horiuchi
Izumi
I
Araki
Norie
N
Toda
Tosifusa
T
Araki
Tomohiro
T
Sato
Kaori
K
Murai
Hiroyuki
H
Osoegawa
Manabu
M
Yamada
Takeshi
T
Okamura
Ken
K
Ogino
Tomoaki
T
Mizumoto
Kiyohisa
K
Yamashita
Hirohumi
H
Saya
Hideyuki
H
Kira
Jun-ichi
J
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*
D001323:Autoantibodies; D001324:Autoantigens; D020543:Proteome; D011994:Recombinant Proteins; D010751:Phosphopyruvate Hydratase