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Investigation of predictive markers for diagnosis, severity, and novel therapeutic target factors for lupus nephritis

Research Project

Project/Area Number 20K17451
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionKeio University

Principal Investigator

Saito Shuntaro  慶應義塾大学, 医学部(信濃町), 助教 (60626381)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords糸球体腎炎 / 全身性エリテマトーデス / 尿タンパクマーカー / 腎病理スコア / ループス腎炎 / 腎病理 / 病態マーカー / 尿プロテオーム / 腎炎
Outline of Research at the Start

Systemic Lupus Erythematosus (SLE)は、多様な臓器が障害される代表的な自己免疫性疾患である。SLE患者においてその30-60%が腎炎(ループス腎炎)を呈し、その生命予後に大きく影響する。現状ではループス腎炎の診断には侵襲性の高い腎生検を行う以外に有効な手段がなく、ステロイドをはじめとした治療は副作用リスクも高いことなどから、ループス腎炎の診療には未解決部分が多い。本研究では独自に設定した腎病理スコアリングシステムと、最新の尿プロテオーム解析を含めた免疫学的因子の検討を行い、ループス腎炎の診断/活動性マーカーおよび新規治療ターゲット分子の探索を目的とする。

Outline of Final Research Achievements

We conducted correlation analysis, cluster analysis, and signal analysis on the original renal pathology scores and the proteome proteins, identifying three novel proteins associated with specific renal pathologic features. The results were validated using ELISA and also confirmed in a validation cohort. We also examined differences between lupus nephritis and diabetic nephropathy, confirming disease specificity. Collaboration with the internal intellectual property management department confirmed the patentability, leading to a patent application(2023-13619). We consulted with the MBL company on creating a prototype for an in vitro diagnostic and decided to continue enriching the data. The paper has been written and is currently under review by a leading journal in the rheumatology field.

Academic Significance and Societal Importance of the Research Achievements

全身性エリテマトーデス(SLE)は、本邦では若年女性を中心に約10万人が罹患する、多様な臓器を呈する自己免疫性疾患である。その30-60%がループス腎炎を呈し、その生命予後に大きく影響する。現状ではループス腎炎の診断/重症度分類には侵襲性の高い腎生検を行う以外に有効な手段がなく、ステロイドを含む治療のcomplete responderは20-50%程度でありループス腎炎の診断/重症度評価/治療には未解決の部分が依然として多い。本研究は独自に設定した詳細な腎病理スコアリングシステムと、最新の尿プロテオーム解析を含めた免疫因子の検討を行い、これらの課題解決の一助となるマーカーの探索を目的とした。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (3 results)

All 2023 2022

All Presentation (1 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Presentation] Aptamer-based proteomic screening in identification of pathogenic signal pathway and urinary biomarkers associated with histological findings in lupus nephritis2022

    • Author(s)
      Kazuoto Hiramoto, Shuntaro Saito
    • Organizer
      EULAR 2022, Annual European Congress of Rheumatology
    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 特許権2023

    • Inventor(s)
      齋藤 俊太郎
    • Industrial Property Rights Holder
      齋藤 俊太郎
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許権2023

    • Inventor(s)
      齋藤 俊太郎
    • Industrial Property Rights Holder
      慶應義塾
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2022 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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