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

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17451
• 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: 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
• 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

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.

Free Research Field

臨床免疫学

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。