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.