2019 Fiscal Year Final Research Report
Epitope specific therapy in Graves' disease
| Project/Area Number |
17K09888
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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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| Research Field |
Endocrinology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
Hidefumi Inaba 和歌山県立医科大学, 医学部, 講師 (70447770)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | バセドウ病 |
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| Outline of Final Research Achievements |
The detailed mechanism in the development of Graves’ disease (GD) is unclear. And novel therapies of GD is warranted.We have previously reported that human TSH receptor (AA78-94) was an important epitope.The aim of this study is 1) to elucidate novel epitope presentation in GD as the complex of thymus, HLA, and autoantigen, and 2) to establish various epitope specific therapy for GD.
After the epitope identification study in GD, Hashimoto’s thyroiditis, thyroid dysfunction by immune-checkpoint inhibitors (ICIs), and other endocrine diseases by ICIs, various antigen and disease-specific HLAs were identified.Therapeutic role of the mutant human TSH receptor peptide: 37m, was evaluated in this study. GD model of HLA-DR3 transgenic mice was treated with 37m. The thyrotoxicosis was improved, TRAb production was suppressed, and proportion of regulatory T-cells in the spleen was increased.
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| Free Research Field |
内分泌学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、GD並びにGD眼症に関する各個体における詳細かつ的確な病態解析を行い、将来的に安全かつ効果的な治療の開発を目指すものである。本計画の連続的治療戦略は中枢性並びに末梢性免疫抑制を組み合わせており、全身的免疫異常を制御できる。また、治療が困難であり時に致死的でさえあるGDの加療において長期的かつ根本的な治癒をもたらす可能性がある。また、本治療法の確立が、難治性自己免疫疾患に関する治療法の発展につながる。
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