Dysregulation of immune response in murine IgA nephropathy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Juntendo University
• Principal Investigator: Kihara Masao 順天堂大学, 医学部, 准教授 (50512604)
• Co-Investigator(Kenkyū-buntansha): 鈴木 仁 順天堂大学, 医学部, 准教授 (10468572) ; 鈴木 祐介 順天堂大学, 医学(系)研究科(研究院), 教授 (70372935)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 粘膜免疫応答異常 / 糖鎖異常IgA / IgG-IgA 免疫複合体 / NALT / GALT

Outline of Final Research Achievements

Levels of aberrantly glycosylated IgA and IgA-IgG immune complexes (IC) in serum and supernatant from cultured MLN and splenocytes were measured using IgAN onset and quiescent ddY mice. levels of aberrantly glycosylated IgA and IgA-IgG IC in IgAN onset ddY mice were significantly higher than those in quiescent ddY mice. However, there were no significant differences in the levels of aberrantly glycosylated IgA and IgA-IgG IC produced by MLN between IgAN onset and quiescent mice. Serum levels of aberrantly glycosylated IgA and IgA-IgG IC correlated with those in culture supernatant of splenocytes. However, the sugar component of IgA produced by MLN was different from those in circulation in IgAN onset ddY mice. Furthermore, serum IgA-IgG IC levels did not associate with those levels produced by cultured MLN. Thus, IgA originated from GALT did not form immune complexes with IgG due to the differentiated glycosylation pattern.

Free Research Field

腎臓

Academic Significance and Societal Importance of the Research Achievements

特に本邦において、IgA腎症の扁桃摘出の有効性など、扁桃とIgA腎症の関連は多数報告されており、IgA腎症は扁桃病巣感染症の１つであると広く認識されている。その一方、現在欧州で行われているNEFIGAN TRIALで、腸管選択的ステロイドのIgA腎症に対する有効性が報告された。本研究においては腸管由来のIgAは血清や脾臓とは糖鎖修飾パターンが異なることで免疫複合体を作らないと考えられ、IgA腎症の発症に関与しない可能性が示された。しかし、IgA腎症と炎症性腸疾患との合併や腸炎によって尿所見の増悪を認める症例もあることから、腸管粘膜とIgA腎症において、さらなる検討が必要である。