Development of diagnosis and treatment approaches for Familial Mediterranean Fever using iPS cells
Project/Area Number |
17K16255
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
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Research Institution | Kyoto University |
Principal Investigator |
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Research Collaborator |
Nishikomori Ryuta
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Project Period (FY) |
2017-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 家族性地中海熱 / サイトカイン / iPS細胞 / 変異機能評価 / 免疫学 / 小児科学 / 診断法 / 自己炎症性疾患 |
Outline of Final Research Achievements |
Through experiments with patient-derived samples, we revealed that monocytes and macrophages derived from Familial Mediterranean Fever (FMF) patients show distinctive phenotypes. While colchicine failed to inhibit IL-1b secretion from patients' monocytes, it inhibited IL-1b secretion from patients' macrophages. In addition, patients' macrophages secreted higher levels of IL-1b than controls. We next obtained macrophages from patient-derived iPS cells, and found that they recapitulated the characteristices of peripheral blood-derived macrophages. Finally, we established genetically-engineered macrophages that expressed MEFV variants with undetemined pathogenecity, and evaluated the presence or absence of IL-1b hypersecretion. By this approach, we established the platform to evaluate various MEFV variants.
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Academic Significance and Societal Importance of the Research Achievements |
MEFV変異は300近く同定されているが、これまでは患者数の多い変異でしか5つしかFMF発症との関連が証明されていなかった。本研究では日本の2家系で同定されているN679Hが新たにFMF発症と関連があることを証明した。われわれが開発した方法を用いることにより、疾患原性の有無が不明なMEFV変異がFMF発症に寄与しているかどうかを明らかにすることができる。これまでは疾患原性が不明な患者ではコルヒチン試験投与への反応性でFMFかどうかの診断がなされていたが、将来的には遺伝子変異が同定された時点でFMFかどうか診断される症例が増えることが予想される。
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Report
(3 results)
Research Products
(9 results)
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[Presentation] Differential activation of the pyrin inflammasome in monocytes and macrophages predicts the pathological significance of MEFV variants in familial Mediterranean fever (FMF) patients2019
Author(s)
Takeshi Shiba1, T. Tanaka1, H. Ida2, M. Watanabe1, H. Nakaseko4, M. Osawa5, H. Shibata1, K. Izawa1, T. Yasumi1, Y. Kawasaki5, M. K.Saito5, J. Takita1, T. Heike6, R. Nishikomori1
Organizer
10th Biannual Meeting of the International Society of Systemic Auto-Inflammatory Diseases
Related Report
Int'l Joint Research
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