Mechanisms of glomerular injuries and complement activity by galactose-deficient IgA1-containing immune complexes.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17292
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Juntendo University
• Principal Investigator: Makita Yuko 順天堂大学, 医学部, 非常勤助教 (20838487)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: IgA腎症 / 糖鎖異常IgA1

Outline of Final Research Achievements

To elucidate the pathogenesis of IgA nephropathy, we investigated the mechanism of renal tissue damage caused by galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1 immune complex (IC). The results suggest that Gd-IgA1 IC shows high affinity to glomerular endothelial cells and causes glomerular endothelial cell damage, resulting in glomerular filtration barrier dysfunction and inducing IgA deposition and complement activation in the mesangial region. Furthermore, Gd-IgA1 IC promoted the production of adhesion factors and inflammatory cytokines in glomerular endothelial cells, suggesting that Gd-IgA1 IC-induced glomerular endothelial cell damage is involved in the pathogenesis of IgA nephropathy.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

IgA腎症は世界で最も頻度が高い原発性糸球体腎炎であるが、IgA腎症の原因となる免疫系の異常が特定されておらず、有効な治療法が確立されていない予後不良な疾患である。その病態には糖鎖異常IgA1(Gd-IgA1)とその免疫複合体(IC)が深く関与することが示唆されている。本研究では、Gd-IgA1 ICによって糸球体内皮細胞障害、補体活性化が誘導され、腎炎が増悪することが示唆された。IgA腎症の病態が解明されることにより、新たなIgA腎症治療法の開発が期待される。