Elucidation of the pathogenesis of autoinflammatory syndromes using patient samples and iPS cells caused by various MEFV variants

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08320
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto University
• Principal Investigator: TANAKA TAKAYUKI 京都大学, 医学研究科, 客員研究員 (20625678)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 家族性地中海熱 / 遺伝子検査 / 遺伝子多型 / MEFV

Outline of Final Research Achievements

We evaluated cell death of THP-1 cells, a human monocytic cell line, after transfection of GFP-labelled various MEFV variants. Pathogenic M694V variant induced stronger cell death compared to WT MEFV. We evaluated 32 MEFV variants with this method. Hierarchical clustering divided the variants into 6 clusters. This grouping correlated well with clinical phenotypes of each variant. Therefore, we established a method of MEFV variants evaluation that does not need patient-derived samples, and published as a research paper.

Free Research Field

自己炎症性疾患

Academic Significance and Societal Importance of the Research Achievements

家族性地中海熱の原因遺伝子であるMEFVは多種の遺伝子多型があり、検査で見付かっても評価が困難でしたが、MEFV多型を分類する手法を開発しました。特に患者さんの血液を必要とせず、実験室だけで完了することができる点が本法の利点です。MEFV遺伝子検査後にどう判断し、治療するかという場面において、それぞれのMEFV多型の意義を正確に判断できるようになり、臨床的にメリットが大きいと考えられます。