Proteomic analysis of human brain identifies α-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 (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.