Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis has diverse patterns of injury including microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Necrotizing and crescentic glomerulonephritis (NCGN) occurs in all syndromes and as renal limited vasculitis (RLV). Single-dose intravenous ANCA IgG-specific for mouse myeloperoxidase (MPO) causes RLV in mice. Although multiple mouse models have elucidated ANCA–IgG induced necrotizing and crescentic glomerulonephritis (NCGN), pathogenesis of ANCA-induced granulomatosis and vasculitis outside the kidney has not been clarified. To investigate this, we used intravenous MPO-ANCA IgG in the same strain of mice to induce different patterns of lung disease mirroring patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Repeated intravenous MPO-ANCA IgG induced GPA with NCGN, lung capillaritis, arteritis and granulomatosis. Lung leukocyte phenotypes were evaluated by immunohistochemical image analysis and by flow cytometry. ANCA lung capillaritis and microabscesses began within one day and evolved into granulomas in under seven days. Influenza plus single-dose MPO-ANCA IgG induced MPA with NCGN, lung capillaritis and arteritis, but no granulomatosis. Allergic airway disease caused by house dust mites or ovalbumin plus single-dose intravenous MPO-ANCA IgG induced EGPA with eosinophilic bronchiolitis, NCGN, capillaritis, arteritis, and granulomatosis. Thus, our study shows that the occurrence and pattern of lung lesions are determined by the same ANCA IgG accompanied by different synergistic immune factors.

中文翻译：

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髓过氧化物酶-ANCA IgG 根据协同免疫刺激的类型诱导不同形式的小血管炎


抗中性粒细胞胞质自身抗体 （ANCA） 血管炎有多种损伤类型，包括显微镜下多血管炎 （MPA）、肉芽肿性多血管炎 （GPA） 和嗜酸性肉芽肿性多血管炎 （EGPA）。坏死性和新月体性肾小球肾炎 （NCGN） 见于所有综合征和肾局限性血管炎 （RLV）。小鼠髓过氧化物酶 （MPO） 的单剂量静脉注射 ANCA IgG 特异性可引起小鼠的 RLV。尽管多种小鼠模型已经阐明了 ANCA-IgG 诱导的坏死和新月体肾小球肾炎 （NCGN），但 ANCA 诱导的肉芽肿和肾外血管炎的发病机制尚未阐明。为了研究这一点，我们在同一品系小鼠中使用静脉注射 MPO-ANCA IgG 来诱导不同模式的肺部疾病，反映了肉芽肿性多血管炎 （GPA） 、显微镜下多血管炎 （MPA） 和嗜酸性肉芽肿性多血管炎 （EGPA） 患者。重复静脉注射 MPO-ANCA IgG 诱导的 GPA 伴 NCGN、肺毛细血管炎、动脉炎和肉芽肿病。通过免疫组织化学图像分析和流式细胞术评估肺白细胞表型。ANCA 肺毛细血管炎和微脓肿在 1 天内开始，并在 7 天内演变为肉芽肿。流感加单剂量 MPO-ANCA IgG 诱导 MPA 伴 NCGN、肺毛细血管炎和动脉炎，但无肉芽肿。由屋尘螨或卵清蛋白加单剂量静脉注射 MPO-ANCA IgG 诱导的 EGPA 伴嗜酸性粒细胞性细支气管炎、NCGN、毛细血管炎、动脉炎和肉芽肿病引起的过敏性气道疾病。因此，我们的研究表明，肺部病变的发生和模式是由相同的 ANCA IgG 伴随着不同的协同免疫因子决定的。