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

Abstract

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.

• Authors: Casey Jo Anne Smith, Sophie Bensing, Christine Burns, Phillip J Robinson, Anna A Kasperlik-Zaluska, Rodney J Scott, Olle Kämpe, Patricia A Crock
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 166 Issue 3 Pg. 391-8 (Mar 2012) ISSN: 1479-683X [Electronic] England
• PMID: 22193973 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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