Pathogenesis of Anti-PIT-1 Antibody Syndrome: PIT-1 Presentation by HLA Class I on Anterior Pituitary Cells.

Abstract

CONTEXT:

Anti-pituitary-specific transcriptional factor-1 (anti-PIT-1) antibody syndrome is characterized by acquired and specific deficiencies in growth hormone, prolactin, and thyroid-stimulating hormone. Although PIT-1-reactive cytotoxic T lymphocytes (CTLs) have been speculated to recognize anterior pituitary cells and to cause the injury in the pathogenesis of the syndrome, it remains unclear whether endogenous PIT-1 protein is processed through the proteolytic pathway and presented as an antigen on anterior pituitary cells.

OBJECTIVE:

To examine how PIT-1 protein is processed and whether its epitope is presented by major histocompatibility complex (MHC)/HLA class I on anterior pituitary cells.

MATERIALS AND METHODS:

Immunofluorescence staining and proximity ligation assay (PLA) were performed using anti-PIT-1 antibody and patients' sera on PIT-1-expressing cell line GH3 cells and human induced pluripotent stem cell (iPSC)-derived pituitary tissues.

RESULTS:

PIT-1 was colocalized with MHC class I molecules, calnexin, and GM130 in the cytosol. PLA results showed that PIT-1 epitope was presented by MHC/HLA class I molecules on the cell surface of GH3 cells and iPSC-derived pituitary cells. The number of PIT-1/HLA complexes on the cell surface of pituitary cells in the patient was comparable with that in the control subject.

CONCLUSIONS:

Our data indicate that PIT-1 protein is processed in the antigen presentation pathway and that its epitopes are presented by in MHC/HLA class I on anterior pituitary cells, supporting the hypothesis that PIT-1-reactive CTLs caused the cell-specific damage. It is also suggested that number of epitope presentation was not associated with the pathogenesis of anti-PIT-1 antibody syndrome.

• Authors: Keitaro Kanie, Hironori Bando, Genzo Iguchi, Keiko Muguruma, Ryusaku Matsumoto, Ryoko Hidaka-Takeno, Yasuhiko Okimura, Masaaki Yamamoto, Yasunori Fujita, Hidenori Fukuoka, Kenichi Yoshida, Kentaro Suda, Hitoshi Nishizawa, Wataru Ogawa, Yutaka Takahashi
• Journal: Journal of the Endocrine Society (J Endocr Soc) Vol. 3 Issue 11 Pg. 1969-1978 (Nov 01 2019) ISSN: 2472-1972 [Electronic] United States
• PMID: 31620667 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Endocrine Society.