| Project/Area Number |
17K16218
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
Kubo Satoshi 産業医科大学, 医学部, 助教 (70461548)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 強皮症 / 爪郭部毛細血管顕微鏡 / 免疫フェノタイプ / 肺動脈性肺高血圧症 / 間質性肺疾患 / 肺動脈性高血圧症 / リンパ球 / 臨床 / 免疫 |
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| Outline of Final Research Achievements |
Peripheral blood mononuclear cells obtained from 150 SSc patients were used for comprehensive flow cytometric analysis. Hierarchical cluster analysis stratified SSc patients into three groups: patients with few immune abnormalities, high proportions of activated T and Treg cells, and patients with high proportions of Tfh and plasmablasts (Tfh-dominant group). Microvascular abnormalities, especially the “late” nailfold videocapillaroscopy (NVC) pattern, correlated with internal organ involvement. Among the groups stratified according to immune cell phenotype, the progression to the “late” NVC pattern was more frequent in the Tfh-dominant group.
In conclusion, our study confirmed the presence of immunophenotypic abnormalities in SSc. Immunological abnormalities were not uniform but rather limited to subpopulations, particularly the Tfh-dominant group, where they were highly associated with microvascular abnormalities and organ involvement.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により強皮症の免疫フェノタイプ異常と強皮症患者の細分化が示された。免疫学的異常は強皮症患者で均一ではなく、免疫フェノタイプの相違により細分化することにより、爪郭部毛細血管顕微鏡で検出した血管障害の進行や臓器障害の併発に関連するサブグループが存在することが明らかになり、そのサブグループが濾胞性T細胞が優位な免疫フェノタイプを有することが示された。このような試みによるエビデンスの蓄積は、強皮症の病態解明のみならず治療への応用、precision medicineの実現が期待される。
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