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Epitope analysis of myeloperoxdase-specific anti-neutrophil

髓过氧化物酶特异性抗中性粒细胞表位分析

基本信息

批准号：
08670265
负责人：
SUZUKI Kazuo
金额：
$ 1.47万
依托单位：
National Institute of Infectious Diseases
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

Autoantibody, myeloperoxidase-specific anti-neutrophul cytoplasmic antibody (MPO-ANCA) has been detected in vasculitis. However, it appears that the titer of MPO-ANCA does not always reflect the activity of the disease. This apparent inconsistency may be mainly attributed to different epitope recognition by MPO-ANCA among sera of the patients. Epitope analysis of MPO-ANCA may explain the correlation between the disease activity and the production of MPO-ANCA.Moreover, mouse anti-MPO antibody induces superoxide production of neutrophils activated with TNFC? though FcRII.These observations suggest that MPO-ANCA recognizes MPO molecule on the surface of patients, neutrophils with specific epitope and stimulates them though FcRII.In order to understand the activation of neutrophils of the patients related with severity of the diseases, epitope of MPO-ANCA should be analyzed. Epitope mapping of autoantibodies using recombinant fragments have been established as a panel for examining reactivity with sera from patients of MPO-ANCA-related diseases. Epitope analysis of sera of patients with MPO-ANCA-related renal diseases and vasculitis was conducted by Western blotting and ELISA using a panel set of recombinant deletion mutants of MPO.Most of the sera reacted with either of the region of N- or C- terminus of the heavy chain, whereas no serum reacted with the light chain regions. The reactivity to the specific sites decreased in the serv of patients with pulmonary fibrosis, alveolar hemorrhage and rapidly progressive glomerulonephritis. Moreover, the epitope profiles showing the oligo-clonality were classified to two and four groups. The profiles had relation with clinical features of the diseases. When score was estimated by the classification of epitope, it was related with the severity of these clinical features. Further, we analyzed the epitopes of MPO-ANCA of patients with Kawasaki Disease.

自身抗体，髓过氧化物酶特异性抗中性粒细胞胞浆抗体（MPO-ANCA）已在血管炎中检测到。然而，MPO-ANCA的滴度似乎并不总是反映疾病的活动性。这种明显的不一致可能主要是由于患者血清中MPO-ANCA对表位的识别不同。MPO-ANCA的表位分析可以解释疾病活动性与MPO-ANCA的产生之间的相关性。此外，小鼠抗mpo抗体诱导TNFC激活的中性粒细胞产生超氧化物。尽管FcRII。这些观察结果表明，MPO- anca可以识别具有特定表位的患者中性粒细胞表面的MPO分子，并通过FcRII刺激它们。为了了解与疾病严重程度相关的患者中性粒细胞活化情况，需要对MPO-ANCA表位进行分析。利用重组片段对自身抗体进行表位定位已被建立为一种检测与mpo - anca相关疾病患者血清反应性的方法。采用Western blotting和ELISA对MPO- anca相关肾脏疾病和血管炎患者的血清进行表位分析，采用一组重组MPO缺失突变体。大多数血清与重链的N端或C端发生反应，而与轻链区域没有反应。在肺纤维化、肺泡出血和快速进行性肾小球肾炎患者中，特异部位的反应性降低。此外，显示寡克隆的表位谱可分为2组和4组。这些特征与疾病的临床特征有关。当通过表位的分类来估计评分时，它与这些临床特征的严重程度有关。进一步，我们分析了川崎病患者MPO-ANCA的表位。