Pathogenetic roles of anti-DNA antibodies in systemic lupus erythematosus

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07821
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kubota Tetsuo 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (90205138)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 全身性エリテマトーデス / 抗DNA抗体 / 精神神経ループス

Outline of Final Research Achievements

In systemic lupus erythematosus, various autoantibodies including those reactive with DNA are produced. This study aimed to clarify the pathogenetic role of the anti-DNA antibodies. In a previous study, we have shown that a monoclonal anti-DNA antibody WB-6, which is cross-reactive with phospholipid, enters monocytes and induces tissue factor expression and a pro-thrombotic state. Currently, we demonstrated that the TLR9 pathway is the main pathway in this process. In another study, we have shown that a dsDNA-specific monoclonal antibody 2C10 enters monocytes and induces expression of IFN-alpha, IFN-beta, TNF-alpha by peripheral blood mononuclear cells. Currently, we extended these results and tested if these anti-DNA antibodies also enter live cells in the brain. As a result, we observed that WB-6 entered the cytoplasm and 2C10 entered the nucleus of rat primary culture astrocytes.

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)の病態形成機構の一つとして，抗DNA抗体とDNAの免疫複合体がエンドサイトーシスで細胞内に取り込まれ，自然免疫のDNAセンサーを刺激してサイトカイン産生などが誘発されることが示唆されている．しかし，中枢神経系の細胞にもこのような機構が当てはまるか否かについてはほとんど知見がない．本研究は抗DNA抗体がアストロサイトにも能動的に取り込まれることを示したもので，SLEにしばしば見られる精神神経症状の発症機構の解明につながる重要な情報を提供するものである．