Suzuki Kazuo, Kobayashi Shigeto, Yamazaki Kazushige, Gondo Masaaki, Tomizawa Kazuo, Arimura Yoshihiro, Nakabayashi Kimimasa, Ozaki Shoichi, Yoshida Masaharu, Yoshida Toshiharu, Tsusaka Norimasa, Muso Eri, Okazaki Tomio, Hashimoto Hiroshi
Laboratory of Biodefense, Department of Bioactive Molecules, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
Microbiol Immunol. 2007;51(12):1215-20. doi: 10.1111/j.1348-0421.2007.tb04017.x.
Autoantibodies to myeloperoxidase (MPO) are a subset of anti-neutrophil cytoplasmic antibody (ANCA, MPO-ANCA) detected in the sera of some patients with primary systemic vasculitis. The titer of MPO-ANCA does not always reflect disease activity and this inconsistency may be attributable to differences in epitopic specificity by MPO-ANCA among various patients with vasculitis. Epitope analysis may also explain the occurrence of MPO-ANCA in different vasculitic syndromes. We screened the sera of 148 MPO-ANCA positive patients from six vasculitic syndromes: rapidly progressive gromerulonephritis (RPGN), microscopic polyangiitis (MPA), idiopathic crescentic glomerulonephritis (I-CrGN), classic polyangiitis nodosa (cPAN), Churg-Strauss syndrome (CSS), Kawasaki disease (KD); and from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The sera were collected by the Intractable Vasculitis Research Project Group in Japan. No serum showed epitopes La and Lb of light chain of MPO, and sera with 68.6% of patients showed a positive reaction to one or more epitopes in heavy chain of MPO. Analysis of binding level showed that RPGN, I-CrGN and MPA sera mainly reacted to the Ha epitope at the N-termimus of the MPO heavy chain, CSS sera reacted to Ha and the Hf epitope close to the C-terminus of the MPO heavy chain, KD reacted mainly to Hf, while SLE and RA sera reacted to all epitopes. These results suggest that MPO-ANCA recognizing specific regions of the N-terminus of the MPO H-chain confer an increased risk of vasculitis RPGN, I-CrGN, MPA and CSS. Furthermore, the epitopic specificity of MPO-ANCA differentiates vasculitic from non-vasculitic syndromes associated with MPO-ANCA positivity and differentiates in the cirtain type of vasculitis from various vasculitic syndromes. In particular, vasculitic syndromes associated with kidney involvement had similar epitopic reactivity which suggests that this pattern confers an increased risk of vasculitis.
髓过氧化物酶（MPO）自身抗体是在一些原发性系统性血管炎患者血清中检测到的抗中性粒细胞胞浆抗体（ANCA，MPO-ANCA）的一个亚群。MPO-ANCA的滴度并不总是反映疾病活动度，这种不一致可能归因于不同血管炎患者中MPO-ANCA表位特异性的差异。表位分析也可能解释MPO-ANCA在不同血管炎综合征中的出现情况。我们筛选了来自六种血管炎综合征的148例MPO-ANCA阳性患者的血清，这六种综合征分别为：急进性肾小球肾炎（RPGN）、显微镜下多血管炎（MPA）、特发性新月体性肾小球肾炎（I-CrGN）、典型结节性多血管炎（cPAN）、变应性肉芽肿性血管炎（CSS）、川崎病（KD）；还包括类风湿关节炎（RA）和系统性红斑狼疮（SLE）患者的血清。这些血清由日本难治性血管炎研究项目组收集。没有血清显示出MPO轻链的La和Lb表位，68.6%的患者血清对MPO重链中的一个或多个表位呈阳性反应。结合水平分析表明，RPGN、I-CrGN和MPA血清主要与MPO重链N端的Ha表位反应，CSS血清与Ha以及MPO重链C端附近的Hf表位反应，KD主要与Hf反应，而SLE和RA血清与所有表位反应。这些结果表明，识别MPO重链N端特定区域的MPO-ANCA会增加患血管炎RPGN、I-CrGN、MPA和CSS的风险。此外，MPO-ANCA的表位特异性区分了与MPO-ANCA阳性相关的血管炎和非血管炎综合征，并在某些类型的血管炎中区分了不同的血管炎综合征。特别是，与肾脏受累相关的血管炎综合征具有相似的表位反应性，这表明这种模式会增加患血管炎的风险。
