Proposal of anti-moesin as a novel biomarker for ANCA-associated vasculitis
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Updated: May 7, 2026
Supervised Machine Learning for Semi-Quantification of Extracellular DNA in Glomerulonephritis
Published on: June 18, 2020
Kazuo Suzuki1,2,3, Koya Suzuki4,5,6, Tomokazu Nagao4
1Inflammation Program, Graduate School of Medicine, Chiba University, Inohana 1-8-15, Chuou-ku, Chiba, 260-8670, Japan. ksuzuki@nih.go.jp.
Abstract:
Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) in microscopic polyangiitis (MPA). MPO-ANCA activates neutrophils by binding to cell surface MPO expressed on tumor necrosis factor-α (TNF-α)-primed neutrophils and induces neutrophil degranulation and production of reactive oxygen species, consequently resulting in glomerular endothelial damage. Recently, anti-MPO antibody has been found to activate glomerular endothelial cells, leading to an upregulation of adhesion molecules. MPO-ANCA, however, is not always correlated with disease activity in MPA. Accordingly, the molecule(s) responsible for the anti-MPO antibody have been explored on mouse glomerular endothelial cells. The molecule was identified as moesin, which is a heparin-binding protein and belongs to the ezrin/radixin/moesin family of proteins distributed in the plasma membrane in the cellular cortex. Interestingly, anti-moesin is observed in sera of SCG/Kj mice, which spontaneously develop MPO-ANCA-associated RPGN, and of patients with MPO-AAV. The activation of glomerular endothelial cells by the anti-MPO antibody appears to be associated with signaling through moesin.
Insights
Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA) triggers neutrophil activation, leading to kidney damage in microscopic polyangiitis (MPA). Researchers identified moesin as a key molecule involved in this MPO-ANCA-mediated endothelial cell activation.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Myeloperoxidase (MPO)-specific antineutrophil cytoplasmic antibody (ANCA) is linked to rapidly progressive glomerulonephritis (RPGN) in microscopic polyangiitis (MPA).
- MPO-ANCA activates neutrophils, causing glomerular endothelial damage, but its correlation with disease activity is inconsistent.
- Previous studies suggest anti-MPO antibodies activate glomerular endothelial cells, upregulating adhesion molecules.
Purpose of the Study:
- To identify the specific molecule(s) on mouse glomerular endothelial cells targeted by anti-MPO antibodies.
- To elucidate the mechanism of MPO-ANCA-induced glomerular endothelial cell activation.
Main Methods:
- Utilized mouse glomerular endothelial cells to investigate molecular targets of anti-MPO antibodies.
- Analyzed sera from SCG/Kj mice and patients with MPO-ANCA-associated vasculitis (MPO-AAV).
- Investigated the role of moesin in anti-MPO antibody-mediated endothelial cell signaling.
Main Results:
- Moesin, a heparin-binding protein of the ezrin/radixin/moesin family, was identified as a key molecule on glomerular endothelial cells.
- Anti-moesin antibodies were detected in SCG/Kj mice with spontaneous MPO-ANCA-associated RPGN and in patients with MPO-AAV.
- Endothelial cell activation by anti-MPO antibodies appears to involve signaling pathways mediated by moesin.
Conclusions:
- Moesin is a critical target molecule for anti-MPO antibodies in MPO-ANCA-associated glomerulonephritis.
- The interaction between anti-MPO antibodies and moesin on glomerular endothelial cells contributes to disease pathogenesis.
- Targeting moesin-mediated signaling may offer a therapeutic strategy for MPO-ANCA-associated RPGN.
