Mechanism of abnormally glycosylated IgA production in the palatine tonsil

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22915
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Fujita Health University
• Principal Investigator: Ohyama Yukako 藤田医科大学, 医学部, 講師 (70879717)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: IgA腎症 / O結合型糖鎖 / 口蓋扁桃 / 形質細胞

Outline of Final Research Achievements

From previous studies, we have found that patients with IgA nephropathy (IgAN) are characterized by increased blood levels of IgA1 with a reduced number of O-glycans (O-glycan decreased-IgA1). In this study, we aimed to clarify the role of the palatine tonsil as the production source of mother of production of IgA1 with abnormal glycan structures. The study revealed that patients with chronic tonsillitis without nephropathy have an increased percentage of O-glycan decreased IgA1 in their serum, similar to patients with IgAN, but that IgA levels are further increased in patients with IgAN. In the palatine tonsils, the percentage of IgA-producing plasma cells was found to be increased compared to patients with chronic tonsillitis. It is predicted that migration of IgA-producing plasma cells from the palatine tonsils into the bloodstream is involved in the pathogenesis of the disease.

Free Research Field

IgA腎症

Academic Significance and Societal Importance of the Research Achievements

近年IgA腎症の治療薬としてLong lived plasma cellをターゲットにした抗CD38モノクローナル抗体の臨床治験が開始されている。本研究によって得られた、IgA腎症患者口蓋扁桃中IgA産生形質細胞増加は、扁桃摘出術だけでなくこうした治療薬の有用性を裏付ける可能性がある。我々は、最終年度に、フローサイトメトリーを用いて、IgA形質細胞中Long lived plasma cell (LLPC)サブセットを解析する手法を確立した。IgA産生Long lived plasma cellについては生理的・病態的意義について未解明な点が多いため、さらに詳細な検証が期待される。