Comprehensive analysis of commensal microbiota involved in the development of IgA nephropathy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08234
• 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: Niigata University
• Principal Investigator: Goto Shin 新潟大学, 医歯学系, 准教授 (00463969)
• Co-Investigator(Kenkyū-buntansha): 成田 一衛 新潟大学, 医歯学系, 教授 (20272817)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: IgA腎症 / 扁桃 / IgA-SEQ / IgAレパトア / マイクロバイオーム / 糖鎖不全IgA1

Outline of Final Research Achievements

The interplay between mucosal immunity and microbiota in patients with IgA nephropathy (IgAN) is considered to underlie disease pathogenesis. We conducted this study to elucidate the mechanisms underlying the mucosal immune response to microbiota at the tonsillar crypts and its role in the development of IgAN.
Expression of immune cell activating factor in tonsillar crypts was elevated in patients with IgAN, correlating with the expression of the distinct IgA repertoire in IgA1 at the tonsillar crypts. Bacteria from the phylum Bacteroidetes were highly coated with IgA at the tonsillar crypts of IgAN patients, correlating with the tonsillar expression of the repertoire in IgA1. Serum polymeric IgA, comprising high levels of galactose-deficient IgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. This study strengthens the role of the mucosal immune response to microbiota in the pathogenesis of IgAN.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究からIgA腎症患者の粘膜免疫異常について、特に扁桃組織において細菌叢に対するIgAの反応性が明らかとなった。IgA腎症は指定難病であり、治療として扁桃摘出術およびステロイド治療が広く行われている。扁桃摘出の理論的根拠として局所の粘膜免疫異常を示したことは実際の臨床診療に意義があると思われる。さらに治療ターゲットとなるメカニズムの解明が期待される。