ANTI-NEUTROPHIL CYTOPLASMIC AUTOANTIBODIES WITH SPECIFICITY FOR MYELOPEROXIDASE IN PATIENTS WITH SYSTEMIC VASCULITIS AND IDIOPATHIC NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS
ANTI-NEUTROPHIL CYTOPLASMIC AUTOANTIBODIES WITH SPECIFICITY FOR MYELOPEROXIDASE IN PATIENTS WITH SYSTEMIC VASCULITIS AND IDIOPATHIC NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS
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DOI：
10.1056/nejm198806233182504
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发表时间：
1988-06-23
影响因子：
158.5
通讯作者：
JENNETTE, JC
中科院分区：
文献类型：
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作者：
FALK, RJ;JENNETTE, JC
在系统性大动脉炎和肾小球肾炎患者中已发现抗中性粒细胞胞浆自身抗体。我们研究了这些自身抗体的疾病分布和抗原特异性。在35例特发性坏死性和新月体肾炎患者中，27例用间接免疫荧光显微镜检测到抗中性粒细胞胞浆自身抗体。自身抗体的发生率和滴度在仅限于肾脏疾病的患者和有全身疾病的患者之间没有差异。11例狼疮性肾炎患者中有5例检测到抗中性粒细胞免疫染色，71例其他肾脏疾病患者中有4例检测到抗中性粒细胞免疫染色，50例正常对照组均未检测到抗中性粒细胞免疫染色。以中性粒细胞裂解物为抗原的酶联免疫吸附试验证实了自身抗体的这种分布。根据酶联免疫吸附试验，发现抗中性粒细胞胞浆抗体是针对初级颗粒成分的。我们鉴定了两种类型的自身抗体：一种是与髓过氧化物酶反应的自身抗体，产生酒精固定的中性粒细胞的人工核周免疫染色；另一种是与髓过氧化物酶不反应的自身抗体，产生弥漫性胞浆免疫染色。同一血清标志物在肾局限性动脉炎相关性坏死性和新月体肾炎患者中的存在，包括韦格纳S肉芽肿和结节性多动脉炎，提示这些临床上不同的疾病可能有相似的发病机制，由自身抗体介导的中性粒细胞激活启动。
Anti-neutrophil cytoplasmic autoantibodies have been found in patients with systemic arteritis and glomerulonephritis. We studied the disease distribution and antigen specificity of these autoantibodies. Anti-neutrophil cytoplasmic autoantibodies were identified by indirect immunofluorescence microscopy in 27 of 35 patiens with idiopathic necrotizing and crescentic glomerulonephritis, in whom the manifestations of disease ranged from injury limited to the kidney to systemic arteritis. The incidence and titers of the autoantibodies did not differ between patients with disease limited to the kidney and those with systemic disease. Anti-neutrophil immunostaining was detected in 5 of 11 patients with lupus nephritis, 4 of 71 patients with other renal diseases, and none of 50 normal controls. This distribution of autoantibodies was confirmed by an enzyme-linked immunosorbent assay (ELISA) using neutrophil lysate as antigen. According to ELISA, anti-neutrophil cytoplasmic autoantibodies were found to be specific for constituents of primary granules. Two types of autoantibodies were identified; one with reactivity with myeloperoxidase on ELISA produced an artifactual perinuclear immunostaining of alcohol-fixed neutrophils, and another with no reactivity with myeloperoxidase on ELISA produced diffuse cytoplasmic immunostaining. The presence of the same serologic marker in patients with kidney-limited and arteritis-associated necrotizing and crescentic glomerulonephritis, including Wegener''s granulomatosis and polyarteritis nodosa, suggests that these clinically diverse diseases may have a similar pathogenesis, initiated by autoantibody-mediated activation of neutrophils.