Hewins P, Tervaert J W, Savage C O, Kallenberg C G
Division of Medical Sciences, MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Edgbaston, UK.
Curr Opin Rheumatol. 2000 Jan;12(1):3-10. doi: 10.1097/00002281-200001000-00002.
Wegener's granulomatosis is a multisystem disease characterized by granulomata of the respiratory tract and systemic necrotising vasculitis. There is a strong and specific association with autoantibodies directed against proteinase 3, a constituent of neutrophril azurophilic granules. Antibody titers correlate with clinical disease activity and predict relapses. The disease responds favorably to immunosuppressive therapy. The pathogenicity of antineutrophil cytoplasmic antibodies (ANCA), however, remains unproven. In vitro, the expression of proteinase-3 and other ANCA antigens on the surface of neutrophils and monocytes can be induced by priming with proinflammatory cytokines. Antineutrophil cytoplasmic antibodies are then able to activate these leukocytes, stimulating degranulation, the production of reactive oxygen species, and the secretion of further cytokines. Neutrophils activated by ANCA, and possibly ANCA alone, directly damage endothelial cells in vitro. An animal model of proteinase 3-ANCA-induced vasculitis has not been found. Antineutrophil cytoplasmic antibodies directed against another antigen, myeloperoxidase, are not sufficient to cause vasculitis but they promote damage in certain animal models. Thus, a considerable amount of evidence supports the notion that Wegener's granulomatosis is an autoimmune disease.
韦格纳肉芽肿病是一种多系统疾病，其特征为呼吸道肉芽肿和系统性坏死性血管炎。它与针对蛋白酶3（中性粒细胞嗜天青颗粒的一种成分）的自身抗体存在强烈且特定的关联。抗体滴度与临床疾病活动度相关，并可预测复发情况。该疾病对免疫抑制治疗反应良好。然而，抗中性粒细胞胞浆抗体（ANCA）的致病性仍未得到证实。在体外，用促炎细胞因子预处理可诱导中性粒细胞和单核细胞表面蛋白酶-3及其他ANCA抗原的表达。抗中性粒细胞胞浆抗体随后能够激活这些白细胞，刺激脱颗粒、活性氧的产生以及进一步细胞因子的分泌。由ANCA激活的中性粒细胞，可能还有单独的ANCA，在体外可直接损伤内皮细胞。尚未发现蛋白酶3-ANCA诱导的血管炎动物模型。针对另一种抗原髓过氧化物酶的抗中性粒细胞胞浆抗体不足以引发血管炎，但在某些动物模型中它们会促进损伤。因此，大量证据支持韦格纳肉芽肿病是一种自身免疫性疾病这一观点。
