The pathophysiological analysis of novel Ďanti-PIT-1 antibody syndrome'

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 164-196-Pituitary
Basic/Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-196
Genzo Iguchi*1, Hironori Bando2, Masaaki Yamamoto2, Ryoko Takeno2, Kentaro Suda2, Michiko Takahashi2, Hitoshi Nishizawa2, Hidenori Fukuoka1 and Yutaka Takahashi2
1Kobe University Hospital, Kobe, Japan, 2Kobe Univ Graduate School of Med, Kobe, Japan
The pituitary-specific transcriptional factor-1 (PIT-1, also known as POU1F1), plays a pivotal role in regulating the expressions of growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH). Recently, we have reported a novel ‘anti-PIT-1 antibody syndrome’ in which 3 adult patients with acquired CPHD exhibiting GH, PRL, and TSH deficiencies were specifically associated with circulating anti-PIT-1 antibodies (1). Although, a presence of anti-PIT-1 antibody indicates autoimmunity to PIT-1, it is unclear that PIT-1 protein is a direct target of this antibody because PIT-1 is a nuclear protein. To clarify the pathogenesis of this syndrome, we determined the epitope of the antibody using a phage display system and examined a presence of PIT-1-reactive T cells by ELISPOT assay. An epitope screening using phage display revealed that two distinct epitopes, which localize in transactivation domain and POU homeodomain in the PIT-1 protein, were recognized by the antibody. Intriguingly, while incubation with the antibody to GH3 cells did not affect the transcriptional activity of PIT-1 in vitro, the ELISPOT assay using isolated lymphocytes demonstrated a presence of PIT-1-reactive cytotoxic T cells in the patient with ‘anti-PIT-1 antibody syndrome’, suggesting that specific impairment of PIT-1-expressing cells was caused by the cytotoxic T cells. It is hypothesized that immune intolerance to PIT-1 occurred with still unknown mechanisms, thereby provoking the attack of PIT-1-expressing pituitary cells by cytotoxic T cells through recognition of PIT-1 epitopes exposed with HLA on the cell surface. These results indicate that immune tolerance to PIT-1 was impaired not only in B cells but also in T cells in the patient and may explain the pathogenesis of ‘anti-PIT-1 antibody syndrome’.

(1) Yamamoto M et al., J Clin Invest. 2011;121:113

Nothing to Disclose: GI, HB, MY, RT, KS, MT, HN, HF, YT

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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