Investigation for clinical application of phospholipase D4 in autoimmune diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08475
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Kyoto University
• Principal Investigator: Akizuki Shuji 京都大学, 医学研究科, 助教 (50626637)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ホスホリパーゼD4 / 全身性自己免疫疾患

Outline of Final Research Achievements

Phospholipase D4 (PLD4) is a susceptibility gene for diseases such as rheumatoid arthritis and functions as an exonuclease that suppresses the TLR7 and TLR9 pathways intracellularly. On the other hand, extracellular PLD4 is present at high concentrations in human plasma, suggesting that abnormalities in extracellular nucleic acid metabolism may contribute to autoimmune diseases. In 2022, an attempt was made to quantify soluble PLD4 using ELISA, but it was found that the anti-human PLD4 antibody did not recognize PLD4 derived from mammalian cells. Therefore, the antibody's reactivity was confirmed using a Western blot with HEK293T cells, and soluble PLD4 was created as a positive control for ELISA, but no reaction was detected in the ELISA. Continuing efforts are being made to establish a quantification system for soluble PLD4 by changing the antibody type, exploring its potential as a biomarker for autoimmune diseases.

Free Research Field

臨床免疫学

Academic Significance and Societal Importance of the Research Achievements

関節リウマチ、全身性エリテマトーデスを含む膠原病性疾患の病態は依然として未知が多い。本研究課題は膠原病性疾患の遺伝的原因を起点とし、同定された新規の疾患感受性遺伝子の1つであり、DAN/RNAヌクレアーゼであるホスホリパーゼD4に着目し、疾患の原因から臨床応用への展開を目的とした。核酸代謝障害はこれら疾患の病態形成の上流を形成すると考えられているが、バイオマーカー、治療標的としては未確立である。本研究課題を通じ、核酸代謝を標的とした臨床応用の基盤となることが期待される。