Pathophysiology of recurrent IgA nephropathy after renal transplantation by analysis of abnormal O-glycans of immortalized B cell-produced IgA

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16734
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Osaka University
• Principal Investigator: Nakazawa Shigeaki 大阪大学, 医学系研究科, 特任助教(常勤) (80759530)
• Project Period (FY): 2021-03-01 – 2022-03-31
• Keywords: IgA腎症 / 腎移植 / O型糖鎖 / 不死化B細胞下部

Outline of Final Research Achievements

In the present study, glycan analysis using an immortalized B cell line isolated from a patient revealed that PNA binding was significantly lower in patients with IgA nephropathy than in healthy controls. This means that sialic acid is bound to many of the Core1 O glycans. The glycosyltransferase that binds sialic acid to Core1 is ST3GAL1, and the expression of ST3GAL1 was significantly elevated in IgA nephropathy patients compared to healthy controls. Therefore, knockout of ST3GAL1 in an immortalized B cell line targeting ST3GAL1 restored cell surface PNA binding to a level comparable to that of healthy individuals.
On the other hand, there was no significant difference in HPA lectin binding between IgA nephropathy patients and healthy controls, which had been considered important.

Free Research Field

腎移植

Academic Significance and Societal Importance of the Research Achievements

IgA腎症にシアル酸が関連しているかについてはこれまでほとんど報告がなかった。本研究によりIgA腎症の病態においてST3GAL1が重要な役割を担っている可能性が示唆された。またこれまで難しかった不死化B細胞下部のシングルセルソーティングに成功し、現在疾患特異的なIgA糖鎖構造解析を進行中である。本研究によってST3GAL1をターゲットとした新規治療法の開発につなげれれば、難病疾患指定であるIgA腎症の治療法の開発に大きな光となる可能性がある。