The remission strategy of ANCA-associated vasculitis through the recovery from immune aging

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08455
• 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: Shinshu University
• Principal Investigator: Shimojima Yasuhiro 信州大学, 学術研究院医学系, 准教授 (50436896)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ANCA関連血管炎 / BAFF / APRIL

Outline of Final Research Achievements

The purpose of our study was to clarify the efficacy of Sirt1 activation for regulating B-cell activation factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) in ANCA-associated vasculitis (AAV). However, no significant suppression of intracellular BAFF and APRIL expression in CD14+ cells was observed by the induction of Sirt1 and redox reaction of resveratrol (RVL). Meanwhile, increased intracellular expression of BAFF and APRIL, which was significantly correlated with the reduction of SOCS3, was demonstrated after the treatment with RVL. Moreover, phosphorylated STAT1 and STAT3 were simultaneously promoted in RVL-treated CD14+ cells. Our study suggests that SOCS3-STAT1/STAT3 signal is implicated in overproduction of BAFF and APRIL in AAV.

Free Research Field

膠原病

Academic Significance and Societal Importance of the Research Achievements

全身性エリテマトーデスではBAFFに対する中和抗体薬（ベリムマブ）が保険収載されているが、AAVではベリムマブの臨床効果が期待できない検証結果が報告された。申請者は、APRILもAAV患者の自己反応性B細胞の発現に寄与して病態に深く関わることを解明し、BAFFとAPRILをともに制御することがAAVの寛解維持に重要であることを報告した。膠原病患者のBAFF/APRIL産生細胞に着目した研究は類がなく、BAFFとAPRILの双方を産生細胞レベルで制御すればAAVの病態に即した疾患修飾療法になると確信する。