2018 Fiscal Year Final Research Report
Investigation of molecular mechanism and therapeutic target of Chronic Mucocutaneous Candidiasis
| Project/Area Number |
16H05355
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Hiroshima University |
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Principal Investigator |
OKADA SATOSHI 広島大学, 医系科学研究科(医), 講師 (80457241)
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| Co-Investigator(Kenkyū-buntansha) |
津村 弥来 広島大学, 医歯薬保健学研究科(医), 研究員 (80646274)
山本 卓 広島大学, 理学研究科, 教授 (90244102)
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| Research Collaborator |
OHARA osamu
ASANO takaki
NISHIMURA shiho
SAITO satoshi
SAKATA sonoko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 慢性皮膚粘膜カンジダ症 / STAT1機能獲得型変異 / IL17RA / 造血細胞移植 / 疾患モデルマウス |
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| Outline of Final Research Achievements |
We systematically investigated patients with gain-of-function (GOF) mutation in STAT1 that explain more than half of the patients with chronic mucocutaneous candidiasis (CMCD). We conducted questionnaire based international survey of patients with STAT1-GOF mutations and revealed that the patients show broad infectious and non-infectious manifestations. We next investigated patients with severe clinical manifestation who were treated with haematopoietic stem cell transplantation (HSCT). This study revealed that HSCT can be a curable treatment, but it has a significant risk of death. We also established reference database which can predict functional significance of uncharacterized amino acid substitution in STAT1. Simultaneously, we generated disease model mouse by generating R274Q STAT1-GOF mutation knock in mouse.
As for the CMCD patients without STAT1 mutation, we identified patients with IL17RA deficiency and characterized clinical manifestation of this disorder.
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| Free Research Field |
感染免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
研究成果のうち学術的に意義深い点は以下の３点と考えられる。本研究により、1) STAT1遺伝子に認めたアミノ酸置換の病的意義が容易となった点、2) 本症の病態解明・治療法の開発に役立つ疾患モデルマウスを確立できた点、3) IL17RA異常症という疾患概念を確立できた点。
また本研究で、STAT1-GOF変異を持つ患者の臨床症状を明らかとするとともに、本症患者に対する造血幹細胞移植の有用性・問題点を解明することができた。この2点は、STAT1-GOF変異を持つ患者の診療に直結する成果であり、非常に大きな社会的意義を持つと考えらえる。
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