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

• 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
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• 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 / 扁桃陰窩 / レパトア解析 / 口蓋扁桃 / IgA-Seq / メタ16S解析

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.

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。

Research Products

• [Journal Article] Aberrant mucosal immunoreaction to tonsillar microbiota in immunoglobulin A nephropathy (2021)
  • Author(s): Hiroki Yamaguchi, Shin Goto, Nao Takahashi, Masafumi Tsuchida, Hirofumi Watanabe, Suguru Yamamoto, Yoshikatsu Kaneko, Koichi Higashi, Hiroshi Mori, Yukio Nakamura, Arata Horii, Ken Kurokawa, Ichiei Narita
  • Journal Title: Nephrol Dial Transplant. Volume: ３６ Issue: 1 Pages: 75-86
  • DOI: 10.1093/ndt/gfaa223
  • Peer Reviewed / Open Access
• [Presentation] IgA腎症患者の扁桃陰窩におけるIgAレパトアとIgA結合細菌叢の関連 (2020)
  • Author(s): 山口 浩毅、 後藤 眞、 山本 卓、 金子 佳賢、 成田 一衛
  • Organizer: 第63回日本腎臓学会学術総会
• [Presentation] IgA腎症患者の口蓋扁桃陰窩におけるIgA結合細菌群と糖鎖不全IgA1. (2019)
  • Author(s): 山口浩毅、 後藤眞、 山本卓、 金子佳賢、 成田一衛.
  • Organizer: 第62回日本腎臓学会学術総会
• [Presentation] 28.Aberrant Immune Response to Periodontopathic Microbiota in Patients with IgA Nephropathy. (2019)
  • Author(s): Hiroki Yamaguchi, Shin Goto, Masafumi Tsuchida, Hirofumi Watanabe, Suguru Yamamoto, Yoshikatsu Kaneko, Ichiei Narita.
  • Organizer: ASN Kidney Week 2019
  • Int'l Joint Research
• [Presentation] Galactose-deficient IgA1 expressed in tonsillar crypts correlates with the severity of glomerular injury in patients with IgA nephropathy (2018)
  • Author(s): Hiroki Yamaguchi, Shin Goto, Masafumi Tsuchida, Hirofumi Watanabe, Suguru Yamamoto, Yoshikatsu Kaneko, Ichiei Narita.
  • Organizer: 第61回日本腎臓学会学術総会
• [Presentation] Immune Response to Tonsillar Microbiome Are Perturbed in the Development of IgA Nephropathy (2018)
  • Author(s): Hiroki Yamaguchi, Shin Goto, Masataka Yonezawa, Masafumi Tsuchida, Hirofumi Watanabe, Suguru Yamamoto, Yoshikatsu Kaneko, Ichiei Narita
  • Organizer: 2018 Kidney Week
  • Int'l Joint Research