Anti-neutrophil cytoplasmic antibodies associated vasculitides (AAV) are characterized by autoimmune small vessel inflammation. Eosinophils are multifunctional cells with both pro-inflammatory and immunoregulatory properties. Tissue activated eosinophils secrete cyto- and chemokines and form extracellular traps (EETs), they release free granules and produce reactive oxygen species. The role of eosinophils is well established in eosinophilic granulomatosis with polyangiitis (EGPA) but very little is known about their role in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The expression of surface markers CD11c, CD11b, CD16, CD35, CD62L, CD64, CD88, Siglec-8 and CD193 and reactive oxygen species production by peripheral blood eosinophils were studied using flow cytometry. Fluorescence microscopy was used to visualize the release of eosinophil extracellular DNA traps (EETs). 98 GPA and MPA patients and 121 healthy controls were included in the study. Both GPA and MPA patients had decreased frequency of eosinophils in peripheral blood compared with healthy controls (p < 0.0001), which could not solely be explained by corticosteroid treatment. The patient’s eosinophils showed increased surface expression of the Fc receptors CD16 (p < 0.0001) and CD64 (p = 0.0035) as well as CCR3 (CD193) (p = 0.0022). Decreased expression was found of the complement receptors CD35 (p = 0.0022), CD88 (p < 0,0001) as well as CD11c (p < 0,0001), CD11b (p = 0.0061) and Siglec-8 (p = 0,0015). Moreover, GPA and MPA eosinophils, showed decreased capacity to produce ROS (p < 0.0001). ANCA stimulation of eosinophils from GPA and MPA patients after C5a priming enhanced EETosis (p = 0,0088). The percentage of eosinophils were decreased in peripheral blood in GPA and MPA patients and showed altered surface marker expression and function. The enhanced EETosis after ANCA stimulation, suggests that eosinophil can contribute to the autoantibody driven inflammatory process.

中文翻译：

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抗中性粒细胞胞浆抗体相关性血管炎中的嗜酸性粒细胞

抗中性粒细胞胞浆抗体相关血管炎 (AAV) 的特征是自身免疫性小血管炎症。嗜酸性粒细胞是具有促炎和免疫调节特性的多功能细胞。组织活化的嗜酸性粒细胞分泌细胞因子和趋化因子并形成细胞外陷阱 (EET)，它们释放游离颗粒并产生活性氧。嗜酸性粒细胞在嗜酸性肉芽肿伴多血管炎 (EGPA) 中的作用已得到充分证实，但对其在肉芽肿伴多血管炎 (GPA) 和显微镜下多血管炎 (MPA) 中的作用知之甚少。使用流式细胞术研究了表面标志物 CD11c、CD11b、CD16、CD35、CD62L、CD64、CD88、Siglec-8 和 CD193 的表达以及外周血嗜酸性粒细胞产生的活性氧。荧光显微镜用于可视化嗜酸性粒细胞胞外 DNA 陷阱 (EET) 的释放。98 名 GPA 和 MPA 患者以及 121 名健康对照者被纳入研究。与健康对照组相比，GPA 和 MPA 患者外周血中嗜酸性粒细胞的频率降低（p < 0.0001），这不能仅用皮质类固醇治疗来解释。患者的嗜酸性粒细胞显示 Fc 受体 CD16 (p < 0.0001) 和 CD64 (p = 0.0035) 以及 CCR3 (CD193) (p = 0.0022) 的表面表达增加。发现补体受体 CD35 (p = 0.0022)、CD88 (p < 0,0001) 以及 CD11c (p < 0,0001)、CD11b (p = 0.0061) 和 Siglec-8 (p = 0, 0015)。此外，GPA 和 MPA 嗜酸性粒细胞产生 ROS 的能力降低（p < 0.0001）。C5a 启动后 GPA 和 MPA 患者的嗜酸性粒细胞的 ANCA 刺激增强了 EETosis (p = 0,0088)。GPA 和 MPA 患者外周血中嗜酸性粒细胞的百分比降低，并显示出表面标志物表达和功能的改变。ANCA 刺激后 EETosis 增强表明嗜酸性粒细胞可促进自身抗体驱动的炎症过程。