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Identification of the 49-kDa Autoantigen Associated with Lymphocytic Hypophysitis as -Enolase

Pediatric Endocrine Unit, John Hunter Children’s Hospital, University of Newcastle (D.T.O., P.A.C.), Newcastle, New South Wales 2310; Peptide Biology Laboratory, Baker Medical Research Institute (A.I.S., M.L.M.), Prahran, Victoria 3181; Department of Biological Sciences, University of Wollongong (N.M.A., M.R.), Wollongong, New South Wales 2522; and Cell Signaling Unit, Children’s Medical Research Institute (P.J.R.), Westmead, New South Wales 2145, Australia

Address all correspondence and requests for reprints to: Dr. Patricia Crock, John Hunter Children’s Hospital, Locked Bag 1, Newcastle 2310, New South Wales, Australia. E-mail: pcrock{at}mail.newcastle.edu.au

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 -enolase. The identification was confirmed using sera from patients with pituitary autoimmunity, which strongly reacted with recombinant human -enolase and yeast enolase, but not with rabbit muscle ß- enolase. This indicates that the immunoreactive epitopes are largely conserved from yeast to human, but are not present in ß-enolase. -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 -enolase as an autoantigen in lymphocytic hypophysitis.

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