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.
Inflammation Program, Chiba University, Graduate School of Medicine, Chiba City, Japan.
Nephrol Dial Transplant. 2014 Jun;29(6):1168-77. doi: 10.1093/ndt/gft469. Epub 2013 Dec 5.
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.
The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system.
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.
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.
抗髓过氧化物酶（MPO）自身抗体（ANCA）是 MPO-ANCA 相关性血管炎（MPO-AAV）的诊断标准之一，但并不总是与疾病活动相关。在这里，我们在患者血清中检测到针对位于刺激后内皮细胞表面的肌动蛋白结合蛋白（moesin）的自身抗体。
通过 ELISA 评估抗 moesin 自身抗体滴度。通过 Bio-Plex 系统测量 17 种细胞因子/趋化因子。
抗 moesin 自身抗体阳性组的血清肌酐高于阴性组。此外，干扰素（IFN）-γ、巨噬细胞趋化蛋白-1（MCP-1）、白细胞介素（IL）-2、IL-7、IL-12p70、IL-13、粒细胞/巨噬细胞集落刺激因子（GM-CSF）和粒细胞集落刺激因子在阳性组中明显升高。此外，IL-7 和 IL-12p70 水平与抗 moesin 自身抗体滴度相关。基于这些发现以及抗 moesin IgG 与中性粒细胞和单核细胞的结合，我们检测到这些细胞分泌 IFN-γ、MCP-1 和 GM-CSF 等细胞因子/趋化因子。
MPO-AAV 患者血清中存在抗 moesin 自身抗体，与针对具有细胞质特征的中性粒细胞的炎症细胞因子/趋化因子的产生有关，这表明抗 moesin 自身抗体有可能通过中性粒细胞和内皮细胞的激活而发展为血管炎。
