A Proteomic Approach To Identify Autoantigens In Hashimoto'S Encephalopathy

Hashimoto's encephalopathy (HE) is a syndrome involving the central nervous system (CNS), characterized by an heterogeneous clinical presentation with neurological and/or neuropsychiatric symptoms associated with high titers of anti-thyroid antibodies. Although the pathogenesis of HE is still unclear, the response to steroid treatment suggests that autoimmune mechanisms may be involved. To date, the role of anti-thyroid IgG as well as the identification of the antigen(s) targeted by IgG remain unknown. We performed a proteomic study on 19 patients with HE and 15 controls based on bidimensional electrophoresis (2D) of human CNS proteins followed by immunoblotting with cerebrospinal fluid (CSF) of patients. The comparative analysis of 2D maps showed that CSF IgG from HE patients specifically recognized 3 spots in a range of pH from 5 to 7 and of MW from 31 to 37 kDa amongst a wide autoreactivity to neural antigens. After mass spectrometry analysis and immunoblotting with specific antibodies, these proteins were identified as dimethylargininase-I (DDAHI) and aldehyde reductase-I (AKRIAI). Almost 90% of HE patients targeted at least one of two isoforms of DDAHI, while few cases recognized AKRIAI. The present findings suggest DDAHI and AKRIAI as biomarkers of HE although further experimental evidence is needed to understand their pathogenetic and diagnostic role, if any. Our 2D proteomic approach appears to be a sensitive and reliable method to assess the autoimmune repertoire in HE, helping to identify potential autoantigens in CSF and sera of HE patients.