Niles J L, McCluskey R T, Ahmad M F, Arnaout M A
Department of Medicine, Massachusetts General Hospital, Charlestown 02129.
Blood. 1989 Nov 1;74(6):1888-93.
Circulating IgG autoantibodies that produce cytoplasmic immunofluorescence staining of ethanol-fixed normal neutrophils have recently been found in a large percentage of patients with active Wegener's granulomatosis. Such autoantibodies are rarely found in other diseases and are therefore virtually diagnostic of Wegener's granulomatosis. The nature of the neutrophil antigen defined by these autoantibodies is controversial and the roles of the antigen and/or autoantibodies in the pathogenesis of Wegener's granulomatosis are unknown. We studied serum samples that produce the cytoplasmic pattern of staining from 10 patients with a diagnosis of Wegener's granulomatosis. By Western blot analysis, all 10 sera reacted with a 29-Kd neutrophil protein (p29). We generated a mouse monoclonal antibody directed against this antigen. The monoclonal antibody produced the same immunofluorescence staining pattern as the serum autoantibodies and was used to affinity-purify p29. The purified antigen had a novel N-terminal sequence homologous to members of the serine proteinase family and bound to radiolabeled diisopropyl fluorophosphate (DFP). We conclude that the neutrophil antigen responsible for the cytoplasmic staining pattern produced by autoantibodies in patients with active Wegener's granulomatosis is a distinctive serine proteinase.
最近发现，在大部分活动性韦格纳肉芽肿患者中存在循环IgG自身抗体，该抗体可使乙醇固定的正常中性粒细胞产生胞质免疫荧光染色。此类自身抗体在其他疾病中很少见，因此实际上可用于诊断韦格纳肉芽肿。这些自身抗体所定义的中性粒细胞抗原的性质存在争议，并且该抗原和/或自身抗体在韦格纳肉芽肿发病机制中的作用尚不清楚。我们研究了10例诊断为韦格纳肉芽肿患者的血清样本，这些样本产生胞质染色模式。通过蛋白质印迹分析，所有10份血清均与一种29-kD的中性粒细胞蛋白（p29）发生反应。我们制备了针对该抗原的小鼠单克隆抗体。该单克隆抗体产生与血清自身抗体相同的免疫荧光染色模式，并用于亲和纯化p29。纯化后的抗原具有与丝氨酸蛋白酶家族成员同源的新的N端序列，并与放射性标记的二异丙基氟磷酸酯（DFP）结合。我们得出结论，在活动性韦格纳肉芽肿患者中，由自身抗体产生胞质染色模式的中性粒细胞抗原是一种独特的丝氨酸蛋白酶。
