Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as alpha-enolase.
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.
O'Dwyer
Damien T
DT
Pediatric Endocrine Unit, John Hunter Children's Hospital, University of Newcastle, Newcastle, New South Wales 2310, Australia.
Smith
A Ian
AI
Matthew
Mary L
ML
Andronicos
Nicholas M
NM
Ranson
Marie
M
Robinson
Phillip J
PJ
Crock
Patricia A
PA
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
D001324:Autoantigens; D020033:Protein Isoforms; D010751:Phosphopyruvate Hydratase