Elucidation of glycosylation form of nephritogenic IgA1 and dysregulation of mucosal immunity in IgA nephropathy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08733
• 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: Muto Masahiro 順天堂大学, 医学部, 助教 (30790076)
• Co-Investigator(Kenkyū-buntansha): 鈴木 祐介 順天堂大学, 大学院医学研究科, 教授 (70372935) ; 鈴木 仁 順天堂大学, 医学部, 教授 (10468572)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: IgA腎症 / 分泌型IgA / 糖鎖異常IgA1

Outline of Final Research Achievements

Aberrantly glycosylated IgA1 and antibodies directed against aberrantly glycosylated IgA1 has been considered as key molecules in the pathogenesis of IgA nephropathy (IgAN). Mucosae have been speculated as one of the major synthesis sites of aberrantly glycosylated IgA1, whereas it remains uncertain. In this study, we demonstrated the presence of secretory component (SC) in aberrantly glycosylated IgA1 purified from serum of patients with IgAN, indicating that aberrantly glycosylated IgA1 originates from mucosae. Our experiments also revealed that the intensity of deposition of SC in glomerulus is associated with the severity of hematuria, suggesting the involvement of SC in the progression of glomerulonephritis. We are now investigating detailed inflammation mechanisms mediated SC in glomerulus.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

今回我々の実験結果より、糖鎖異常IgA1の少なくとも一部が粘膜由来であり、腎糸球体へのSCの沈着の程度が血尿の重症度と関連していることが確認されており、粘膜由来の糖鎖異常IgA1が腎炎の発症・進展に関与していると考えられた。今回の結果は、糖鎖異常IgA1の産生源と考えられる粘膜をターゲットとした治療である口蓋扁桃摘出術や腸管免疫に特異的に作用するステロイド治療 (Budesonide)の理論的根拠になると思われる。現在、腎糸球体におけるSCを介した炎症惹起メカニズムにについて検証を行っているところである。