Proposal of anti-moesin as a novel biomarker for ANCA-associated vasculitis.
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.
Inflammation Program, Graduate School of Medicine, Chiba University, Inohana 1-8-15, Chuou-ku, Chiba, 260-8670, Japan. ksuzuki@nih.go.jp.|Department of Health Protection, Graduate School of Medicine, Teikyo University, Kaga 2-11-1 Itabashi-ku, Tokyo, 173-8605, Japan. ksuzuki@nih.go.jp.|Asia International Institute of Infectious Disease Control, Teikyo University, Kaga 2-11-1 Itabashi-ku, Tokyo, 173-8605, Japan. ksuzuki@nih.go.jp.
Kazuo
K
Suzuki
Inflammation Program, Graduate School of Medicine, Chiba University, Inohana 1-8-15, Chuou-ku, Chiba, 260-8670, Japan.|Laboratory of Biological Science, Graduate School of Frontier Biosciences, and Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan.|Department of Internal Medicine, Graduate School of Frontier Biosciences, and Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka, 565-0871, Japan.
Koya
K
Suzuki
Inflammation Program, Graduate School of Medicine, Chiba University, Inohana 1-8-15, Chuou-ku, Chiba, 260-8670, Japan.
Tomokazu
T
Nagao
Department of Immunology, Graduate School of Medicine, Chiba University, Inohana 1-8-15, Chuou-ku, Chiba, 260-8670, Japan.
Toshinori
T
Nakayama
D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005921:Glomerulonephritis / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000276:immunology*; D011237:Predictive Value of Tests
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D008840:Microfilament Proteins; C071058:moesin