Elucidation of APRIL-mediated immune abnormalities by tonsillar germinal center B cells in the pathogenesis of IgA nephropathy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09713
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Juntendo University
• Principal Investigator: Suzuki Yusuke 順天堂大学, 医学(系)研究科(研究院), 教授 (70372935)
• Co-Investigator(Kenkyū-buntansha): 武藤 正浩 順天堂大学, 医学部, 助教 (30790076)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: IgA腎症 / APRIL / 糖鎖異常IgA / 口蓋扁桃 / B細胞 / 免疫異常

Outline of Final Research Achievements

Previous studies have revealed that IgA antibodies with abnormal glycosylation deposited in the gomerular mesangium in kidney of patients with IgA nephropathy. In recent years, the involvement of a proliferation inducing ligand (APRIL), which is a cytokine involved in the differentiation and survival of plasma cells, has been suggested to be involved in the pathogenesis of IgA nephropathy, however the details have not been clarified. In the present study, we established a culture system that efficiently induces IgA-positive B cells from naive B cells. Using this new culture system, it has become possible to analyze the detailed mechanism by which APRIL produces abnormal glycosilated IgA antibodies.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

IgA腎症の治療において、a proliferation inducing ligand(APRIL)をターゲットとした分子標的治療薬の国際治験が開始され、近年注目されているが、その理論的根拠の詳細は明らかにされていなかった。本研究成果は、口蓋扁桃摘出術、更にはAPRILをターゲットとした分子標的治療薬の理論的根拠や治療適応基準の基礎データ提供につながると考えられる。