Elucidation of pathogenic mechanism of autoimmune pituitary disease and clinical application
| Project/Area Number |
18K08514
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Kobe University |
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Principal Investigator |
Iguchi Genzo 神戸大学, 保健管理センター, 准教授 (60346260)
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| Co-Investigator(Kenkyū-buntansha) |
高橋 裕 神戸大学, 医学研究科, 准教授 (70301281)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 自己免疫性下垂体疾患 / 抗PIT-1下垂体炎 / 腫瘍随伴症候群 / 抗PIT-1 抗体症候群 |
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| Outline of Final Research Achievements |
Elucidation of pathogenic mechanism of autoimmune pituitary disease: Ectopic expression of PIT-1 and infiltration of cytotoxic T cells were observed in the tumor tissue of patients with anti-PIT-1 hypophysitis, indicating that this disease has an aspect as a paraneoplastic syndrome caused by a malignant tumor. The clinical features of isolated ACTH deficiency were classified into three types by adding anti-pituitary antibody analysis, and the true nature of their diversity and the etiology and pathophysiology were clarified. As a tool for analyzing the molecular mechanism of autoimmune pituitary disease, using anti-PIT-1 hypophysitis as a model, we established Pit-1 specific cytotoxic T cell clone and co-cultured it with the patient's iPS cell-derived pituitary gland. As a result, we have succeeded in creating the first in vitro human autoimmune disease model.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、これまで原因が不明であった自己免疫性下垂体疾患の発症メカニズムを多面的に解明した。抗PIT-1下垂体炎が胸腺腫瘍だけでなく悪性腫瘍の患者において発症することを明らかにし、新たな臨床情報をもたらした。ACTH単独欠損症において新たな臨床分類を提唱したことにより、病因に応じた詳細な機序の解明や治療法の選択の可能性へとつながった。さらに、自己免疫性下垂体疾患は疾患モデルがないことが壁となっていたが、世界初のヒトのin vitro自己免疫疾患モデル作成に成功したことにより、本モデルを用いたさらなる解析へと発展することが期待される。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] The impact of adrenal tumor multidisciplinary team meetings on clinical outcomes.2020
Author(s)
Fukuoka H, Shigemura K, Kanzawa M, Kanda T, Yamamoto M, Kitagawa K, Sakamoto M, Iguchi G, Ogawa W, Fujisawa M, Takahashi Y
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Journal Title
Endocrine.
Volume: 69
Issue: 3
Pages: 519-519
DOI
Related Report
Peer Reviewed
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[Journal Article] Share Patients with pheochromocytoma exhibit low aldosterone renin ratio-preliminary reports.2020
Author(s)
Yamada T, Fukuoka H, Hosokawa Y, Odake Y, Yoshida K, Matsumoto R, Bando H, Okada Y, Hirota Y, Iguchi G, Ogawa W, Takahashi Y.
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Journal Title
BMC Endocr Disord.
Volume: 20
Issue: 1
Pages: 140-140
DOI
Related Report
Peer Reviewed
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[Journal Article] Factors correlated with serum insulin-like growth factor-I levels in health check-up subjects.2018
Author(s)
Matsumoto R, Koga M, Kasayama S, Fukuoka H, Iguchi G, Odake Y, Yoshida K, BandoH, Suda K, Nishizawa H, Takahashi M, Ogawa W, Takahashi Y
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Journal Title
Growth Horm IGF Res.
Volume: in press
Pages: 55-60
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Multiple salivary cortisol measurements are a useful tool to optimize metyrapone treatment in patients with Cushing’s syndromes treatment; case presentations.2018
Author(s)
Yoshida K, Fukuoka H, Odake Y, Nakajima S, Tachibana M, Ito J, Hosokawa Y, Yamada T, Miura H, Suematsu N, Matsumoto R, Bando H, Suda K, Nishizawa H, Iguchi G, Ogawa W, Takahashi Y
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Journal Title
Front Endocrinol
Volume: 8
Pages: 375-375
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] ICI関連下垂体炎、1型糖尿病を同時期に発症した一例2020
Author(s)
藤田泰功,合田菜穂,浦井伸,志智大城,蟹江慶太郎,山本雅昭,岡田裕子,廣田勇士,福岡秀規,井口元三,清田尚臣,小川渉,高橋裕
Organizer
第93回日本内分泌学会学術集会
Related Report
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[Presentation] QT延長、致死性不整脈を呈したACTH分泌不全症の3例2020
Author(s)
浦井伸,山本雅昭,福岡秀規,桂由佳梨,内山奏,西本祐希,金谷雅之,志智大城,蟹江慶太郎,藤田泰功,井口元三,小川渉,高橋裕
Organizer
第93回日本内分泌学会学術集会
Related Report
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[Presentation] Cushing病におけるCRH試験反応性に関連する病態の解明2020
Author(s)
志智大城,福岡秀規,浦井伸,蟹江慶太郎,藤田泰功,山本雅昭,井口元三,井下尚子,山田正三,小川渉,高橋裕
Organizer
第57回日本臨床分子医学会学術集会
Related Report
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[Presentation] 疾患iPS細胞/抗原特異的T細胞を用いた抗PIT-1下垂体炎疾患モデルの樹立2020
Author(s)
蟹江慶太郎,井口元三,伊藤剛,喜多山秀一,坂東弘教,六車恵子,松本隆作,山本雅昭,福岡秀規,金子新,小川渉,高橋裕
Organizer
第57回日本臨床分子医学会学術集会
Related Report
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[Presentation] 下垂体卒中を呈したACTH産生下垂体腺腫の1例2019
Author(s)
志智大城, 福岡秀規, 坂本洋一, 蟹江慶太朗, 藤田泰功, 井口元三, 松本隆作, 隅田健太郎, 井下尚子, 山田正三, 小川渉, 高橋裕
Organizer
第92回日本内分泌学会学術総会
Related Report
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[Presentation] ACTH単独欠損症において抗corticotroph抗体の存在は重症度と関連する2019
Author(s)
藤田泰功, 坂東弘教, 井口元三, 飯田啓二, 志智大城, 蟹江慶太郎, 松本隆作, 隅田健太郎, 福岡秀規, 小川渉, 高橋裕
Organizer
第92回日本内分泌学会学術総会
Related Report
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[Presentation] 副腎神経節腫の合併を認めた特発性低ゴナドトロピン性性腺機能低下症の1例2019
Author(s)
高吉倫史, 福岡秀規, 上村憲, 神澤真紀, 重村克巳, 岡田裕子, 廣田勇士, 井口元三, 藤澤正人, 小川渉, 高橋裕
Organizer
第92回日本内分泌学会学術総会
Related Report
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[Presentation] 診断に難渋したTSH単独分泌不全症の一例2018
Author(s)
隅田健太郎,千原和夫,志智大城,蟹江慶太郎,藤田泰功,小武由紀子,坂東弘教,高橋路子,福岡秀規,井口元三,小川渉,高橋裕
Organizer
第28回臨床内分泌代謝update
Related Report
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