Identification of TPIT and other novel autoantigens in lymphocytic hypophysitis: immunoscreening of a pituitary cDNA library and development of immunoprecipitation assays

Eur J Endocrinol. 2012 Mar;166(3):391-8. doi: 10.1530/EJE-11-1015. Epub 2011 Dec 22.


Background: Lymphocytic hypophysitis is an organ-specific autoimmune disease of the pituitary gland. A specific and sensitive serological test currently does not exist to aid in the diagnosis.

Objective: To identify target autoantigens in lymphocytic hypophysitis and develop a diagnostic assay for these proteins.

Design/methods: A pituitary cDNA expression library was immunoscreened using sera from four patients with lymphocytic hypophysitis. Relevant cDNA clones from screening, along with previously identified autoantigens pituitary gland-specific factor 1a and 2 (PGSF1a and PGSF2) and neuron-specific enolase (NSE) were tested in an in vitro transcription and translation immunoprecipitation assay. The corticotroph-specific transcription factor, TPIT, was investigated separately as a candidate autoantigen.

Results: Significantly positive autoantibody reactivity against TPIT was found in 9/86 hypophysitis patients vs 1/90 controls (P = 0.018). The reactivity against TPIT was not specific for lymphocytic hypophysitis with autoantibodies detectable in the sera from patients with other autoimmune endocrine diseases. Autoantibodies were also detected against chromodomain-helicase-DNA binding protein 8, presynaptic cytomatrix protein (piccolo), Ca(2+)-dependent secretion activator, PGSF2 and NSE in serum samples from patients with lymphocytic hypophysitis, but at a frequency that did not differ from healthy controls. Importantly, 8/86 patients with lymphocytic hypophysitis had autoantibodies against any two autoantigens in comparison with 0/90 controls (P = 0.0093).

Conclusions: TPIT, a corticotroph-specific transcription factor, was identified as a target autoantigen in 10.5% of patients with lymphocytic hypophysitis. Further autoantigens related to vesicle processing were also identified as potential autoantigens with different immunoreactivity patterns in patients and controls.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / biosynthesis
  • Autoantigens / genetics*
  • Autoantigens / immunology
  • Autoantigens / isolation & purification
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / genetics*
  • Gene Library*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / immunology
  • Humans
  • Hypopituitarism / diagnosis
  • Hypopituitarism / genetics*
  • Hypopituitarism / immunology
  • Immunoprecipitation / methods
  • Pituitary Gland / immunology
  • Pituitary Gland / pathology
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / immunology


  • Autoantibodies
  • Autoantigens
  • Homeodomain Proteins
  • T-Box Domain Proteins
  • TBX19 protein, human