Rabphilin-3A as a targeted autoantigen in lymphocytic infundibulo-neurohypophysitis

Shintaro Iwama, Yoshihisa Sugimura, Atsushi Kiyota, Takuya Kato, Atsushi Enomoto, Haruyuki Suzuki, Naoko Iwata, Seiji Takeuchi, Kohtaro Nakashima, Hiroshi Takagi, Hisakazu Izumida, Hiroshi Ochiai, Haruki Fujisawa, Hidetaka Suga, Hiroshi Arima, Yoshie Shimoyama, Masahide Takahashi, Hiroshi Nishioka, San E. Ishikawa, Akira ShimatsuPatrizio Caturegli, Yutaka Oiso

Research output: Contribution to journalArticle

Abstract

Context: Central diabetes insipidus (CDI) can be caused by several diseases, but in about half of the patients the etiological diagnosis remains unknown. Lymphocytic infundibulo-neurohypophysitis (LINH) is an increasingly recognized entity among cases of idiopathic CDI; however, the differential diagnosis from other pituitary diseases including tumors can be difficult because of similar clinical and radiological manifestations. The definite diagnosis of LINH requires invasive pituitary biopsy. Objective: The study was designed to identify the autoantigen(s) in LINH and thus develop a diagnostic test based on serum autoantibodies. Design: Rat posterior pituitary lysate was immunoprecipitated with IgGs purified from the sera of patients with LINH or control subjects. The immunoprecipitates were subjected to liquid chromatographytandem mass spectrometry to screen for pituitary autoantigens of LINH. Subsequently, we made recombinant proteins of candidate autoantigens and analyzed autoantibodies in serum by Western blotting. Results: Rabphilin-3A proved to be the most diagnostically useful autoantigen. Anti-rabphilin-3A antibodies were detected in 22 of the 29 (76%) patients (including 4 of the 4 biopsy-proven samples) with LINH and 2 of 18 (11.1%) patients with biopsy-proven lymphocytic adeno-hypophysitis. In contrast, these antibodies were absent in patients with biopsy-proven sellar/suprasellar masses without lymphocytic hypophysitis (n=34), including 18 patients with CDI. Rabphilin-3Awas expressed in posterior pituitary and hypothalamic vasopressin neurons but not anterior pituitary. Conclusions: These results suggest that rabphilin-3A is a major autoantigen in LINH. Autoantibodies to rabphilin-3A may serve as a biomarker for the diagnosis of LINH and be useful for the differential diagnosis in patients with CDI.

Original languageEnglish (US)
Pages (from-to)E946-E954
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number7
DOIs
StatePublished - Jul 1 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Iwama, S., Sugimura, Y., Kiyota, A., Kato, T., Enomoto, A., Suzuki, H., Iwata, N., Takeuchi, S., Nakashima, K., Takagi, H., Izumida, H., Ochiai, H., Fujisawa, H., Suga, H., Arima, H., Shimoyama, Y., Takahashi, M., Nishioka, H., Ishikawa, S. E., ... Oiso, Y. (2015). Rabphilin-3A as a targeted autoantigen in lymphocytic infundibulo-neurohypophysitis. Journal of Clinical Endocrinology and Metabolism, 100(7), E946-E954. https://doi.org/10.1210/jc.2014-4209