2021 Fiscal Year Final Research Report
Development of predictive biomarkers that enable to "cure" rheumatoid arthritis
| Project/Area Number |
19K07940
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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 52010:General internal medicine-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 関節リウマチ / バイオマーカー / 治癒 / 寛解 |
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| Outline of Final Research Achievements |
The aim of this study was to investigate novel biomarker for "Cure" in rheumatoid arthritis (RA). The study was conducted in two phases: biomarker discovery in an early RA registry and analysis of the regulatory mechanisms of osteoclast differentiation. A total of 204 patients were included in the registry, of which IL-4 and IP10 were shown to be indicators of response to treatment in the first 32 patients, and RANTES was shown to be a predictor of prognosis in the early 32 patients. Basic studies showed an effect of CXCL10 on CTLA-4-Ig action, TGFβ1 regulation of osteoclast differentiation, and involvement of activin A and CXCL10 in regulation, leading to the expectation that TGFβ1 would be a therapeutic target and CXCL10 a novel marker. However, the effect of LPS contamination was found during the validation phase, leading to the development of a new removal method using Re-LPS.
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| Free Research Field |
膠原病・リウマチ内科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではCureを目指したバイオマーカーの探索に、臨床的・トランスレーショナル研究と基礎研究の両面からアプローチした。CXCL10のバイオマーカーとしての有用性および測定系におけるLPS除去の重要性が示されるとともに、新たな治療ターゲットとしてのTGFβ1の可能性が示唆された。また副次的成果としてRe-LPSによるLPSコンタミネーションの新たな解決法開発に繋がった。
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