title: Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as alpha-enolase.
abstract: Lymphocytic hypophysitis is part of the spectrum of organ-specific autoimmune diseases, and although its histopathology is well documented, its pathogenesis is unclear. Serum autoantibodies directed against a 49-kDa cytosolic protein are detected by immunoblotting in 70% of patients with biopsy-proven lymphocytic hypophysitis. Here we report the purification and identification of this first target autoantigen in lymphocytic hypophysitis. The autoantigen has a molecular mass of 49 kDa, a cytosolic localization, and a ubiquitous tissue distribution. The 49-kDa protein was purified from monkey brain and human placental cytosol. Limited amino acid sequencing after proteolytic digestion of the human placental protein showed identity with alpha-enolase. The identification was confirmed using sera from patients with pituitary autoimmunity, which strongly reacted with recombinant human alpha-enolase and yeast enolase, but not with rabbit muscle beta- enolase. This indicates that the immunoreactive epitopes are largely conserved from yeast to human, but are not present in beta-enolase. alpha-Enolase autoantibodies are not specific to pituitary autoimmune disease and have been reported in other autoimmune diseases. However, this study is the first to indicate a role for alpha-enolase as an autoantigen in lymphocytic hypophysitis.
authors.affiliation: Pediatric Endocrine Unit, John Hunter Children's Hospital, University of Newcastle, Newcastle, New South Wales 2310, Australia.
authors.forename: Damien T
authors.initials: DT
authors.lastname: O'Dwyer
authors.forename: A Ian
authors.initials: AI
authors.lastname: Smith
authors.forename: Mary L
authors.initials: ML
authors.lastname: Matthew
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Andronicos
authors.forename: Marie
authors.initials: M
authors.lastname: Ranson
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Crock
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D001769:Blood / Q000276:immunology; D003600:Cytosol / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology*; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010751:Phosphopyruvate Hydratase / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D010900:Pituitary Diseases / Q000276:immunology* / Q000473:pathology*; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification; D011817:Rabbits; D012016:Reference Values
chemical_list: D001324:Autoantigens; D020033:Protein Isoforms; D010751:Phosphopyruvate Hydratase