A novel autoantigen in lymphocytic infundibulo-neurohypophysitis

• Project/Area Number: 24591360
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Nagoya University
• Principal Investigator: YOSHIHISA Sugimura 名古屋大学, 医学部附属病院, 講師 (50456670)
• Co-Investigator(Kenkyū-buntansha): OISO Yutaka 名古屋大学, 医学系研究科, 教授 (40203707)
• Co-Investigator(Renkei-kenkyūsha): SASAI Yoshiki 独立行政法人理化学研究所, グループディレクター (20283616) ; NAGASAKI Hiroshi 藤田保健衛生大学, 准教授 (30420384)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: リンパ球性漏斗下垂体後葉炎 / 76kD蛋白 / ES-AVP細胞 / リンパ球性漏斗下垂体後葉 炎モデル / ES-AVPニューロン / リンパ球性漏斗下垂体後葉炎モデル

Outline of Final Research Achievements

Lymphocytic infundibulo-neurohypophysitis (LINH) is an increasingly recognized entity among idiopathic CDI, however, the differential diagnosis from other pituitary diseases including tumors can be difficult due to similar clinical and radiological manifestations. The definite diagnosis of LINH requires invasive pituitary biopsy.We used shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS) on immunoprecipitates obtained from patient sera incubated with posterior pituitary protein lysate, and the results revealed that 76kD protien is an autoantigen in LINH. We further validated this autoantibody as a novel diagnostic marker.To evaluate the role of 76 kD protein in the pathogenesis of LINH,we developed the 76kD protien-immunized mice and observed the pituitary inflammation. In addition, we found that mouse ESC are self-differentiated into AVP neurons that express 76kD protein.

Research Products

• [Journal Article] Identification of the novel autoantigen candidate Rab GDP dissociation inhibitor alpha in isolated adrenocorticotropin deficiency. (2015)
  • Author(s): Kiyota A, Iwama S, Sugimura Y, Takeuchi S, Takagi H, Iwata N, Nakashima K, Suzuki H, Nishioka T, Kato T, Enomoto A, Arima H, Kaibuchi K, Oiso Y
  • Journal Title: Endocr J Volume: 62 Pages: 153-160
  • NAID: 130004700287
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus. (2014)
  • Author(s): Hagiwara D, Arima H, Morishita Y, Wenjun L, Azuma Y, Ito Y, Suga H, Goto M, Banno R, Sugimura Y, Shiota A, Asai N, Takahashi M, Oiso Y
  • Journal Title: Cell Death Dis Volume: 27
  • Peer Reviewed
• [Journal Article] GABA type B receptor signaling in proopiomelanocortin neurons protects against obesity, insulin resistance, and hypothalamic inflammation in male mice on a high-fat diet. (2013)
  • Author(s): Ito Y, Banno R, Shibata M, Adachi K, Hagimoto S, Hagiwara D, Ozawa Y, Goto M, Suga H, Sugimura Y, Bettler B, Oiso Y, Arima H.
  • Journal Title: J Neurosci. Volume: 33 Pages: 17166-73
  • Peer Reviewed
• [Journal Article] Lesion of area postrema attenuated hyperphagic responses to glucoprivation, but not transcriptional activation of the neuropeptide Y gene in rats. (2012)
  • Author(s): Ozawa Y, Arima H, Banno R, Ito Y, Goto M, Morishita Y, Sugimura Y, Ozaki N, Nagasaki H, Oiso Y.
  • Journal Title: Neuroreport. Volume: 23 Issue: 11 Pages: 673-675
  • DOI: 10.1097/wnr.0b013e3283556676
  • Peer Reviewed
• [Presentation] リンパ球性漏斗下垂体後葉炎の診断マーカーの発見 (2013)
  • Author(s): 椙村益久
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター（仙台市）
• [Presentation] Involvement of Rab3a and Rabphilin3a in AVP secretion in ES cell-derived AVP neurons (2013)
  • Author(s): Atsushi Kiyota, Yoshihisa Sugimura, Seiji Takeuchi, Hisakazu Izumida, Hiroshi Ochiai, Haruki Fujisawa, Hiroshi Takagi, Kazuki Fukuoka, Hidetaka Suga, Takashi Watanabe, Hiroshi Nagasaki, Yutaka Oiso
  • Organizer: 第３6回日本神経科学大会
  • Place of Presentation: 京都国際会議場（京都市）
• [Presentation] ES細胞由来AVP産生細胞におけるRab関連タンパク質のAVP分泌への関与 (2013)
  • Author(s): 清田 篤志 , 椙村 益久, 竹内 誠治, 泉田 久和, 藤沢 治樹,高木 博史, 福岡 一貴, 渡辺 崇,長崎 弘,有馬 寛, 大磯 ユタカ
  • Organizer: 第86回日本内分泌学会学術総会
  • Place of Presentation: 仙台国際センター（仙台市）
• [Presentation] Identification of a novel autoantigen and a diagnostic marker of autoimmune hypophysitis (2012)
  • Author(s): Yoshihisa Sugimura, Shintaro Iwama, Atsushi Kiyota, Hiroshi Takagi, Seiji Takeuchi, Hisakazu Izumida , Takuya Kato, Atsushi Enomoto, Yutaka Oiso
  • Organizer: 11th International Congress of Neuroimmunology
  • Place of Presentation: Boston （米国）
• [Presentation] Expression of Ras related proteins in ES cell-derived AVP secreting cells (2012)
  • Author(s): Atsushi Kiyota, Yoshihisa Sugimura, Hiroshi Takagi, Kazuki Fukuoka, Hiroshi Nagasaki, Yutaka Oiso
  • Organizer: 15th International and 14th European Congress of Endocrinology
  • Place of Presentation: Florence （イタリア）
• [Presentation] Overly rapid correction of severe hyponatremia with vasopressin receptor antagonists poses a risk of inducing osmotic demyelination syndrome (2012)
  • Author(s): Hiroshi Takagi, Yoshihisa Sugimura, Haruyuki Suzuki, Atsushi Kiyota, Kazuki Fukuoka, Hiroshi Nagasaki, Yutaka Oiso
  • Organizer: 15th International and 14th European Congress of Endocrinology
  • Place of Presentation: Florence （イタリア）
• [Presentation] Identification of a novel autoantigen and a diagnostic marker in lymphocytic infundibuloneurohypophysitis (LINH) (2012)
  • Author(s): Yoshihisa Sugimura, Shintaro Iwama, Atsushi Kiyota, Hiroshi Takagi, Takuya Kato, Atsushi Enomoto, Yutaka Oiso
  • Organizer: 第３５回日本神経科学大会、Neuroscience 2012
  • Place of Presentation: 名古屋国際会議場 （Nagoya）
• [Presentation] Involvement of Ras related proteins in AVP secretion in ES cell-derived AVP neurons (2012)
  • Author(s): Atsushi Kiyota, Yoshihisa Sugimura, Hiroshi Takagi, Kazuki Fukuoka, Takashi Watanabe, Hiroshi Nagasaki, Yutaka Oiso
  • Organizer: 第３５回日本神経科学大会、Neuroscience 2012
  • Place of Presentation: 名古屋国際会議場 （Nagoya）
• [Presentation] A rapid rise in serum sodium levels due to water diuresis as well as hypertonic saline administration in chronic hyponatremia causes osmotic demyelination syndrome (2012)
  • Author(s): Hiroshi Takagi, Yoshihisa Sugimura, Haruyuki Suzuki, Atsushi Kiyota, Kazuki Fukuoka, Yutaka Oiso
  • Organizer: 第３５回日本神経科学大会、Neuroscience 2012
  • Place of Presentation: 名古屋国際会議場 （Nagoya）
• [Presentation] リンパ球性漏斗下垂体後葉炎 (2012)
  • Author(s): 椙村益久
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場 （Nagoya）
• [Presentation] SIADH (2012)
  • Author(s): 椙村益久
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場 （Nagoya）
• [Book] 医学のあゆみ リンパ球性漏斗下垂体後葉炎の診断マーカー (2013)
  • Author(s): 椙村益久、大磯ユタカ、橋本弘史、上田陽一、村瀬孝司、石川三衛、有馬寛、佐々木成、森下啓明、川渕孝一、矢倉英隆、小西郁生、中村清吾、北川恵、与儀淑恵、植田祥啓、木梨達雄、勝野雅央、山下淳、天谷雅行
  • Publisher: 医歯薬出版株式会社
• [Book] 低ナトリウム血症のすべて 低ナトリウム血症の症状―隠れている症状を探るー (2013)
  • Author(s): 椙村益久
  • Total Pages: 5
  • Publisher: メディカルレビュー社
• [Book] 低ナトリウム血症と骨粗鬆症 (2012)
  • Author(s): 椙村益久、大磯ユタカ
  • Publisher: 科学評論社
• [Book] リンパ球性漏斗下垂体後葉炎 (2012)
  • Author(s): 椙村益久、大磯ユタカ
  • Publisher: 診断と治療社
• [Book] リンパ球性下垂体炎の自己抗体 (2012)
  • Author(s): 椙村益久、大磯ユタカ
  • Publisher: 診断と治療社
• [Patent(Industrial Property Rights)] リンパ球性漏斗下垂体後葉炎のバイオマーカー及びその用途 (2012)
  • Inventor(s): 椙村益久ら
  • Industrial Property Rights Holder: 椙村益久ら
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-11-16
  • Overseas