Identification of Epitopes on Monocytes and Signaling Pathways by Autoantibodies in Systemic Lupus Erythematosus

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17449
• 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: Kitasato University
• Principal Investigator: Matsueda Yu 北里大学, 医学部, 助教 (00623208)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: SLE / 抗RNP抗体 / 抗Sm抗体 / 中枢神経病変

Outline of Final Research Achievements

Although central nervous system (CNS) lesions in Systemic Lupus Erythematosus (SLE) are difficult to treat, their mechanisms remain unclear. Previous studies have reported associations between CNS lesions in SLE and antibodies such as anti-Sm antibodies, anti-RNP antibodies, anti-ribosomal P antibodies, and anti-NMDA receptor antibodies. This study aimed to elucidate the mechanism by which autoantibodies in SLE bind to the surface of monocytes and promote the production of inflammatory cytokines. Flow cytometry and confocal laser microscopy analyses revealed that anti-RNP antibodies exhibit a higher affinity for monocyte binding compared to anti-Sm antibodies. Additionally, increased production of inflammatory cytokines by monocytes, mediated by activation of the NFκB pathways, was suggested. These findings indicate that autoantibodies in SLE may contribute to CNS lesions through monocyte interaction, providing crucial insights for the development of new therapeutic strategies.

Free Research Field

リウマチ膠原病内科学

Academic Significance and Societal Importance of the Research Achievements

本研究にて抗RNP抗体が抗Sm抗体と共に存在することで、NFκB経路の活性化され、単球の炎症性サイトカイン産生の増加することが明らかになった。さらに、この自己抗体の作用はFcレセプターを介さない経路である可能性が示唆された。
これらの結果は、SLE特異的自己抗体による中枢神経病変の発症のメカニズムの一端を明らかにしたものであり、SLEの新たな治療戦略の開発に重要な知見を提供するものである。今後は、自己抗体の単球に対する詳細な作用メカニズムの解明が求められる。