Identification of the 49-kDa autoantigen associated with lymphocytic hypophysitis as α-enolase

Damien T. O'Dwyer, A. Ian Smith, Mary L. Matthew, Nicholas M. Andronicos, Marie Ranson, Phillip J. Robinson, Patricia A. Crock

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109 Citations (Scopus)


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

Original languageEnglish
Pages (from-to)752-757
Number of pages6
JournalThe Journal of Clinical Endocrinology and Metabolism
Issue number2
Publication statusPublished - 28 Feb 2002
Externally publishedYes

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