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Identification of TPIT and other novel autoantigens in lymphocytic hypophysitis : immunoscreening of a pituitary cDNA library and development of immunoprecipitation assays
- Smith, Casey Jo Anne (author)
-
- Bensing, Sophie (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för medicinska vetenskaper
- Burns, Christine (author)
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- Robinson, Phillip J. (author)
- Kasperlik-Zaluska, Anna A. (author)
- Scott, Rodney J. (author)
- Crock, Patricia A. (author)
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- (creator_code:org_t)
- 2012
- 2012
- English.
- In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 166:3, s. 391-398
- Journal article (peer-reviewed)
Abstract
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- 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), Ca2+-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.
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