Locke I C, Leaker B, Cambridge G
Centre for Rheumatology, University College London Medical School, London, UK.
Clin Exp Immunol. 1999 Feb;115(2):369-76. doi: 10.1046/j.1365-2249.1999.00809.x.
Although circulating anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO) are strongly associated with the presence of vasculitis, they have been described in sera from patients with other conditions. High levels of anti-MPO antibodies can also persist in sera from patients with vasculitis despite the achievement of clinical remission. One possible interpretation is that a potentially pathogenic subset of anti-MPO antibodies exists, which is only present in patients with active vasculitis. We therefore compared the characteristics of anti-MPO antibodies in sera from patients with active vasculitis (n = 18) with those present in remission (n = 9) and in a disease control group (n = 10) without clinical evidence of vasculitis. The class, subclass and ability of anti-MPO antibodies from the three groups of patients to recognize three different conformational epitopes were analysed using ELISA-based techniques. The expression of an idiotope, designated 9G4, was also examined. Epitope recognition by anti-MPO antibodies from all patients tested was found to be similar. Sera from patients with active vasculitis showed an over-representation of IgG4 subclass anti-MPO antibodies and a more frequent presence of IgM class anti-MPO antibodies. In disease controls, IgG1 anti-MPO antibodies were predominant. In vitro, neutrophil activation by ANCA has been shown to be dependent on engagement of neutrophil FcgammaRIIa receptors following binding of these autoantibodies to surface-expressed ANCA antigens. We found that active vasculitis may be associated with the presence of circulating anti-MPO antibodies which do not significantly bind this receptor, suggesting that mechanisms other than those dependent on FcgammaRIIa binding should be explored. In addition, the expression of the 9G4 idiotope on anti-MPO antibodies in 60% (12/18) of patients with active vasculitis and 20% (2/10) of disease control patients may indicate a common origin for anti-MPO antibodies in different individuals.
尽管循环中针对髓过氧化物酶（MPO）的抗中性粒细胞胞浆抗体（ANCA）与血管炎的存在密切相关，但在患有其他疾病的患者血清中也有发现。尽管血管炎患者已实现临床缓解，但其血清中抗MPO抗体水平仍可能持续升高。一种可能的解释是，存在一种潜在致病性的抗MPO抗体亚群，仅在活动性血管炎患者中出现。因此，我们比较了活动性血管炎患者（n = 18）、缓解期患者（n = 9）和无血管炎临床证据的疾病对照组（n = 10）血清中抗MPO抗体的特征。使用基于酶联免疫吸附测定（ELISA）的技术分析了三组患者抗MPO抗体的类别、亚类以及识别三种不同构象表位的能力。还检测了一种名为9G4的独特型表位的表达。发现所有检测患者的抗MPO抗体的表位识别情况相似。活动性血管炎患者的血清显示IgG4亚类抗MPO抗体比例过高，且IgM类抗MPO抗体出现频率更高。在疾病对照组中，IgG1抗MPO抗体占主导。在体外，已证明ANCA激活中性粒细胞依赖于这些自身抗体与表面表达的ANCA抗原结合后中性粒细胞FcγRIIa受体的参与。我们发现活动性血管炎可能与循环中抗MPO抗体的存在有关，这些抗体与该受体的结合不显著，这表明应探索除依赖FcγRIIa结合之外的其他机制。此外，60%（12/18）的活动性血管炎患者和20%（2/10）的疾病对照患者抗MPO抗体上9G4独特型表位的表达可能表明不同个体中抗MPO抗体有共同起源。
