Mechanisms of differentiation and homing of aberrantly glycosylated IgA producing cells in the pathogenesis of IgA nephropathy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Juntendo University
• Principal Investigator: Suzuki Hitoshi 順天堂大学, 医学部, 准教授 (10468572)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: IgA腎症 / 粘膜免疫 / 免疫複合体 / ホーミング

Outline of Final Research Achievements

Dysregulation of mucosal immune response is involved in the pathogenesis of IgA nephropathy. However, the whereabouts of the responsible cells involved in the production of glycan abnormality IgA1 have not been identified. In present study, it was clarified that aberrantly glycosylated IgA-producing cells, which are key molecular in the pathophysiology of IgA nephropathy, are mainly desensitized and differentiated in nasopharynx-associated lymphoid tissue (NALT) using a natural onset model of IgA nephropathy. Analysis of homing receptors suggested that aberrantly glycosylated IgA-producing cells sensitized in NALT are homing into the bone marrow and differentiate to long-lived plasma cells.

Free Research Field

IgA腎症

Academic Significance and Societal Importance of the Research Achievements

IgA腎症は世界で最も頻度の高い原発性糸球体腎炎であり、腎糸球体に糖鎖修飾異常を伴ったIgA（糖鎖異常IgA）の沈着を特徴とする。予後不良な疾患であり、指定難病に認定されている。現在、科学的根拠がないまま扁桃摘出あるいは腸管選択的作用型ステロイドを用いた治験などが進行している。本研究成果により、科学的根拠をもった適切な治療ガイドを示すことが可能である。IgA腎症の予後を改善することで透析導入を抑制し、医療費の削減を図ることが可能であると考える。