title: Novel autoantigens recognized by CSF IgG from Hashimoto's encephalitis revealed by a proteomic approach.
abstract: To identify the target of IgG autoimmune response in Hashimoto's encephalopathy (HE), we studied the binding of IgG present in serum and cerebro-spinal fluid (CSF) from six patients with HE and 15 controls to human central nervous system (CNS) white matter antigens by 2D-PAGE and immunoblotting and by immunohistochemistry. We found that CSF IgG from HE patients specifically recognized 3 spots, which were identified as dimethylargininase-I (DDAHI) and aldehyde reductase-I (AKRIAI). DDAHI was present in two isoforms recognized respectively by five and four HE patients; immunohistochemistry with anti-DDAHI antiserum depicted endothelial cells in normal human CNS. AKRIAI was recognized by three HE CSF and this enzyme was widely distributed on neurons and endothelia by immunohistochemistry. IgG from HE CSF immunostained both neuronal and endothelial cells in mouse CNS. The presence of these autoantibodies selectively in the CSF of HE patients may have important diagnostic and pathogenetic implications, since the autoimmune response to these enzymes may lead to vascular and/or neuronal damage, two major mechanisms involved in the pathogenesis of HE.
authors.affiliation: Section of Neurology, Department of Neurological Sciences and Vision, University of Verona, Verona, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gini
authors.forename: Laura
authors.initials: L
authors.lastname: Lovato
authors.forename: Lovato
authors.initials: L
authors.lastname: Laura
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cianti
authors.forename: Cianti
authors.initials: C
authors.lastname: Riccardo
authors.forename: Laura
authors.initials: L
authors.lastname: Cecotti
authors.forename: Cecotti
authors.initials: C
authors.lastname: Laura
authors.forename: Silvia
authors.initials: S
authors.lastname: Marconi
authors.forename: Elena
authors.initials: E
authors.lastname: Anghileri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Armini
authors.forename: Armini
authors.initials: A
authors.lastname: Alessandro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Moretto
authors.forename: Moretto
authors.initials: M
authors.lastname: Giuseppe
authors.forename: Luca
authors.initials: L
authors.lastname: Bini
authors.forename: Bini
authors.initials: B
authors.lastname: Luca
authors.forename: Franco
authors.initials: F
authors.lastname: Ferracci
authors.forename: Ferracci
authors.initials: F
authors.lastname: Franco
authors.forename: Bruno
authors.initials: B
authors.lastname: Bonetti
authors.forename: Bonetti
authors.initials: B
authors.lastname: Bruno
mesh_terms: D000368:Aged; D000449:Aldehyde Reductase / Q000378:metabolism; D000581:Amidohydrolases / Q000378:metabolism; D001324:Autoantigens / Q000134:cerebrospinal fluid / Q000276:immunology*; D001808:Blood Vessels / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D050031:Hashimoto Disease / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*
chemical_list: D001324:Autoantigens; D007074:Immunoglobulin G; D000449:Aldehyde Reductase; D000581:Amidohydrolases; C059999:dimethylargininase