| Project/Area Number |
18K15370
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Tawara Nozomu 熊本大学, 病院, 非常勤診療医師 (00802109)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 孤発性封入体筋炎 / 抗cN1A抗体 / 自己免疫機序 / 蛋白分解機構 / 封入体筋炎 |
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| Outline of Final Research Achievements |
Sporadic inclusion body myositis (sIBM), an intractable myopathy, frequently affects elderly person. Autoantibodies for cytosolic 5'-nucleotidase 1A (cN1A) have been found in the sera from sIBM patients. This study investigated the pathogenic roles of anti-cN1A autoantibodies by active immunization of cN1A peptides. Autoantibodies to the related cN1A peptides were detected in the sera from all the groups injected with the peptides. The peptide-injected groups showed a reduction in body weight changes and exercise capacity. The peptide-injected groups showed an increase in the number of myofibers with internal nuclei and inflammatory infiltrates of CD8-positive cells. Expression levels of p62 and LC3-II were increased in the muscles from the peptide-injected group. Active immunization model of cN1A peptides mimics histological and clinical aspects of sIBM. This murine model provides a useful tool for understanding the pathogenesis of sIBM and for developing new therapeutic strategies.
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| Academic Significance and Societal Importance of the Research Achievements |
我々はsIBMに検出される自己抗体の標的抗原を免疫するマウスを作成し、自己免疫的病態と蛋白分解経路異常との関連性を解明し、本疾患の病態を模した初めてのモデルマウスを確立した。同時に有効な治療法のないsIBMの治療法開発のツールとなり、マウス血清中の本抗体の病原性を再度抗体移入実験によって検証し、抗体除去治療研究も行うことが可能となる。さらにcN1A特異的なT細胞やB細胞を増殖、活性化させ野生型マウスに移入することでcN1A特異的リンパ球の病原性についても検証できる。これらの液性免疫因子および細胞性免疫因子の病原性を深く検証することで、疾患特異的な治療法開発を行うことが可能となる。
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