Understanding the pathogenesis of each responsible antigen and establishing new diagnostic methods in primary membranous nephropathy in Japan.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08239
• 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: Nagoya University
• Principal Investigator: Akiyama Shin'ichi 名古屋大学, 医学系研究科, 特任講師 (20500010)
• Co-Investigator(Kenkyū-buntansha): 丸山 彰一 名古屋大学, 医学系研究科, 教授 (10362253)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 膜性腎症 / ネフローゼ症候群 / 責任抗原 / 自己抗体

Outline of Final Research Achievements

The recent discovery of PLA2R and THSD7A as responsible antigens for primary membranous nephropathy (pMN) in adults has updated the disease concept, suggesting that pMN may be classified into subtypes by responsible antigen. In this study, we worked to elucidate the unknown responsible antigens, and to elucidate the pathogenesis and develop a novel diagnostic method using autoantibodies against PLA2R and THSD7A as indicators. We were unable to identify a novel responsible antigen specific to Japanese pMN patients. For PLA2R-related pMN, antibody concentration at diagnosis is an independent risk factor for worsening renal function, but epitope spreading did not correlate with disease activity. THSD7A-associated pMN had a similar pathogenetic mechanism as PLA2R-associated pMN, and diagnosis using autoantibodies as an indicator was useful.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

近年、一次性膜性腎症の責任抗原の一部が明らかになり、抗原染色や血中自己抗体測定に基づいた鑑別・病勢評価・予後予測ができるようになりつつある。その一方で、一次性膜性腎症の病因となっているすべての責任抗原が同定されたわけではなく、とくに日本人一次性膜性腎症患者では責任抗原が不明なタイプの一次性膜性腎症が多く、既知の責任抗原であるPLA2RやTHSD7Aに関しても病態機序の理解や臨床実態の解明が不十分である。本研究は、これらの課題に対して科学的知見を補強するものであり、本邦のみならず世界中の一次性膜性腎症患者の診療に貢献するなどの学術的および社会的な意義を持っている。