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

• Published in: FEBS letters 2002-09, Vol.528 (1), p.197-202
• Main Authors: Ochi, Hirofumi, Horiuchi, Izumi, Araki, Norie, Toda, Tosifusa, Araki, Tomohiro, Sato, Kaori, Murai, Hiroyuki, Osoegawa, Manabu, Yamada, Takeshi, Okamura, Ken, Ogino, Tomoaki, Mizumoto, Kiyohisa, Yamashita, Hirohumi, Saya, Hideyuki, Kira, Jun-ichi
• Format: Article
• Language: English
• Subjects: 2-DE, two-dimensional gel electrophoresis; Amino Acid Sequence; Antibody Specificity; Autoantibodies - blood; Autoantigen; Autoantigens - genetics; BPB, bromophenol blue; Brain; Brain - enzymology; Brain - immunology; Brain Diseases - enzymology; Brain Diseases - immunology; CBB, Coomassie Brilliant Blue; CNS, central nervous system; Electrophoresis, Gel, Two-Dimensional; HC, healthy subject; HE, Hashimoto's encephalopathy; HT, Hashimoto's thyroiditis; Humans; IPG, immobilized pH gradient; MALDI-TOF, matrix-assisted laser desorption ionization time-of-flight; Molecular Sequence Data; OND, other neurological disorder; Peptide Mapping; Phosphopyruvate Hydratase - genetics; Phosphopyruvate Hydratase - immunology; Proteome; Proteomics; PVDF, polyvinylidene difluoride; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thyroiditis, Autoimmune - enzymology; Thyroiditis, Autoimmune - immunology; Two-dimensional electrophoresis; α-enolase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)03307-0

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 (p I 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.