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- Title
Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis.
- Authors
Iwama, Shintaro; Sugimura, Yoshihisa; Kiyota, Atsushi; Kato, Takuya; Enomoto, Atsushi; Suzuki, Haruyuki; Iwata, Naoko; Takeuchi, Seiji; Nakashima, Kohtaro; Takagi, Hiroshi; Izumida, Hisakazu; Ochiai, Hiroshi; Fujisawa, Haruki; Suga, Hidetaka; Arima, Hiroshi; Shimoyama, Yoshie; Takahashi, Masahide; Nishioka, Hiroshi; Ishikawa, San-E; Shimatsu, Akira
- Abstract
<bold>Context: </bold>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.<bold>Objective: </bold>The study was designed to identify the autoantigen(s) in LINH and thus develop a diagnostic test based on serum autoantibodies.<bold>Design: </bold>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 chromatography-tandem 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.<bold>Results: </bold>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-3A was expressed in posterior pituitary and hypothalamic vasopressin neurons but not anterior pituitary.<bold>Conclusions: </bold>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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2015, Vol 100, Issue 7, pE946
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2014-4209