2023 Fiscal Year Final Research Report
The study of the pathogenesis and possible treatment of ROSAH syndrome, a novel inherited autoinflammatory disease caused by ALPK1 gene mutation.
| Project/Area Number |
21K07847
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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 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
八幡 信代 九州大学, 医学研究院, 准教授 (90315812)
山元 裕之 九州大学, 環境発達医学研究センター, 特任助教 (00710170)
園田 素史 九州大学, 医学研究院, 助教 (00748006)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | ROSAH症候群 / 自己炎症性疾患 / ALPK1 / ADP-heptose / 周期性発熱 / ぶどう膜炎 / 網膜オルガノイド / iPS細胞 |
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| Outline of Final Research Achievements |
The iPS cells derived from patients with ROSAH syndrome carrying ALPK1 mutations were generated. The differentiated monocytes were stimulated with cytokines and with ADP-heptose, the ligand for ALPK1. Patient-derived cells showed an excessive inflammatory responses. In addition, retinal organoids derived from iPS cells were were examined to analyze the causes of ocular inflammation.
The inflammatory cytokines levels were reduced in the serum of the patient treated with anti-TNFa antibodies. White blood cells from patients with ROSAH syndrome also showed an excess inflammatory response to LPS and ADP-heptose stimulation in vitro.
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| Free Research Field |
先天性免疫異常症・遺伝性自己炎症性疾患
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| Academic Significance and Societal Importance of the Research Achievements |
ALPK1遺伝子異常によるROSAH症候群に関し、患者血清、細胞を用いて病態および治療反応性の解析を行った。病状の主座である炎症と眼病変に関する病態解析を行うため、患者由来iPS細胞から単球・網膜への誘導を行いその病態を検討した。病因遺伝子同定からの期間が短く、病因である蛋白のALPK1の機能も不詳である。患者由来検体を用いた本研究は病態のみならず患者治療につながる有用な研究である。
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