Investigation of novel biomarkers by multi-omics analysis of systemic lupus erythematosus

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17892
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Keio University
• Principal Investigator: KIKUCHI Jun 慶應義塾大学, 医学部(信濃町), 助教 (20570881)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 全身性エリテマトーデス / ループス腎炎 / 末梢血免疫細胞

Outline of Final Research Achievements

Initially, we reported that achieving a lupus low disease activity state within 12 months after starting induction therapy in active systemic lupus erythematosus (SLE) patients was associated with clinical outcomes. We then identified changes in peripheral blood immune cells following initiation of induction therapy in active SLE. In particular, we showed that the type of peripheral blood immune cells that fluctuate differed depending on the drug predominantly used as induction therapy. Furthermore, we found that fluctuations in peripheral blood plasmablasts were associated with treatment prognosis. Focusing on lupus nephritis, the analysis of urinary proteins showed that various pathways were associated with the pathogenesis associated with active and interstitial lesions in renal biopsy tissue findings.

Free Research Field

リウマチ・膠原病

Academic Significance and Societal Importance of the Research Achievements

全身性エリテマトーデスは多彩な臓器障害をきたす自己免疫疾患で、難病に指定されている。その病態や治療後の経過における評価指標が不確定であるため本研究を行なった。まず適切な臨床的評価指標として、近年国際的に注目されている低疾患活動性状態を、治療開始後12ヶ月以内に達成することが予後と関連することを世界に先駆けて報告した。また、病態の根幹を成すと考えられている免疫担当細胞の亜分画の変動が、治療薬剤により異なること、治療予後と関連することを明らかにした。さらに、尿蛋白解析と腎生検組織所見との関連解析と合わせて、難治性病態の予測として使用される可能性につながる研究成果を得た。