Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase.
Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase.
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发表时间：
1989-11
期刊：
影响因子：
20.3
通讯作者：
J. Niles;R. McCluskey;MF Ahmad;M. Arnaout
中科院分区：
文献类型：
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作者：
J. Niles;R. McCluskey;MF Ahmad;M. Arnaout
循环IgG自身抗体产生细胞质免疫荧光染色的乙醇固定正常中性粒细胞最近被发现在很大比例的活动性韦格纳肉芽肿患者。这种自身抗体在其他疾病中很少发现，因此实际上是韦格纳肉芽肿病的诊断。这些自身抗体定义的中性粒细胞抗原的性质是有争议的，抗原和/或自身抗体在韦格纳肉芽肿病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病的患者的血清样本，产生细胞质染色模式。通过Western blot分析，所有10份血清均与29-Kd中性粒细胞蛋白（p29）反应。我们制备了一种针对该抗原的小鼠单克隆抗体。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。纯化后的抗原具有新的n端序列，与丝氨酸蛋白酶家族成员同源，并与放射性标记的氟磷酸二异丙基（DFP）结合。我们得出结论，中性粒细胞抗原负责细胞质染色模式产生的自身抗体的韦格纳肉芽肿患者是一个独特的丝氨酸蛋白酶。
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.