Koya Suzuki1, Tomokazu Nagao2, Mitsuyo Itabashi3, Yoshitomo Hamano4, Ryuichi Sugamata2, Yuji Yamazaki5, Wako Yumura4, Sachiko Tsukita5, Pi-Chao Wang6, Toshinori Nakayama7, Kazuo Suzuki8. 1. Inflammation Program, Chiba University, Graduate School of Medicine, Chiba City, Japan Graduate School of Life and Environmental Science, Tsukuba University, Tsukuba, Ibaragi, Japan Laboratory of Biological Science, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 2. Inflammation Program, Chiba University, Graduate School of Medicine, Chiba City, Japan. 3. Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan. 4. Department of Internal Medicine, Jichi University, School of Medicine, Shimotsuke, Tochigi, Japan. 5. Laboratory of Biological Science, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. 6. Graduate School of Life and Environmental Science, Tsukuba University, Tsukuba, Ibaragi, Japan. 7. Department of Immunology, Chiba University, Graduate School of Medicine, Chiba City, Japan. 8. Inflammation Program, Chiba University, Graduate School of Medicine, Chiba City, Japan Asia International Institute of Infectious Disease Control, Department of Health Protection, Graduate School of Medicine, Teikyo University, Tokyo, Japan.
Abstract
BACKGROUND: Antineutrophil cytoplasmic autoantibody (ANCA) directed against myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis (MPO-AAV), does not always correlate with disease activity. Here, we detected autoantibodies against moesin, which was located on the surface of stimulated endothelial cells, in the serum of patients. METHODS: The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system. RESULTS: Serum creatinine in the anti-moesin autoantibody-positive group was higher than that in the negative group. Additionally, interferon (IFN)-γ, macrophage chemotactic peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13, granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor were significantly higher in the positive group. Furthermore, IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer. Based on these findings and the binding of anti-moesin IgG to neutrophils and monocytes, we detected the secretion of cytokines/chemokines such as IFN-γ, MCP-1 and GM-CSF from these cells. CONCLUSIONS: The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti-moesin autoantibody has the possibility to be a novel autoantibody developing vasculitis via neutrophil and endothelial cell activation.
BACKGROUND: Antineutrophil cytoplasmic autoantibody (ANCA) directed against myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis (MPO-AAV), does not always correlate with disease activity. Here, we detected autoantibodies against moesin, which was located on the surface of stimulated endothelial cells, in the serum of patients. METHODS: The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system. RESULTS: Serum creatinine in the anti-moesin autoantibody-positive group was higher than that in the negative group. Additionally, interferon (IFN)-γ, macrophage chemotactic peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13, granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor were significantly higher in the positive group. Furthermore, IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer. Based on these findings and the binding of anti-moesin IgG to neutrophils and monocytes, we detected the secretion of cytokines/chemokines such as IFN-γ, MCP-1 and GM-CSF from these cells. CONCLUSIONS: The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti-moesin autoantibody has the possibility to be a novel autoantibody developing vasculitis via neutrophil and endothelial cell activation.
Authors: Dawn J Caster; Erik A Korte; Michael L Merchant; Jon B Klein; Daniel W Wilkey; Brad H Rovin; Dan J Birmingham; John B Harley; Beth L Cobb; Bahram Namjou; Kenneth R McLeish; David W Powell Journal: Proteomics Clin Appl Date: 2015-06-12 Impact factor: 3.494