Role of TLR9 in the pathogenesis of ANCA-associated vasculitis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07602
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Chiba University
• Principal Investigator: Furuta Shunsuke 千葉大学, 医学部附属病院, 特任講師 (10422221)
• Co-Investigator(Kenkyū-buntansha): 中島 裕史 千葉大学, 大学院医学研究院, 教授 (00322024)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ANCA関連血管炎 / BAFF / APRIL / TLR9

Outline of Final Research Achievements

First, we found serum IL-1Ra, IL-5 and IL-15 levels were increased in ANCA-associated vasculitis (AAV) patients, however, IL-6 level was not increased. Although we originally supposed that TLR9 stimulated B cells and induced to release IL-6 in AAV patients, the results were different. Thus, we focused BAFF and APRIL as other candidates activating NF-KB signaling in B cells in AAV patients. Next, we measured serum BAFF and APRIL levels of AAV patients. We found those were significantly higher in AAV patients than in healthy controls and large vessel vasculitis patients. In addition, we found serum BAFF levels in AAV patients were correlated with serum CRP levels, which were considered as an indicator of the disease activity of AAV.

Free Research Field

膠原病内科学

Academic Significance and Societal Importance of the Research Achievements

今回の結果より、1)AAVの発症にBAFFが重要な役割を果たしていること、2)Rituximabの投与によりAAVは沈静化するがBAFFの発現自体は減少していないことが明らかとなった。AAVの治療において、寛解時にはB細胞除去が重要であるが、その後の再燃に関してはBAFFの発現も考慮に入れるべきであると考えられた。BAFFに対する抗体製剤は既に市販されている（Belimumab、AAVに対しては未承認）。BelimumabはAAVに対する有効性を示せなかったという先行研究も存在するが、今回の結果を踏まえると病期によっては有効な治療選択肢になる可能性がある。