丙硫氧嘧啶诱导的抗中性粒细胞胞浆抗体相关性血管炎中抗髓过氧化物酶抗体的表位分析
Epitope analysis of anti-myeloperoxidase antibodies in propylthiouracil-induced antineutrophil cytoplasmic antibody-associated vasculitis.
作者信息
Wang Chen, Gou Shen-ju, Xu Peng-cheng, Zhao Ming-hui, Chen Min
出版信息
Arthritis Res Ther. 2013;15(6):R196. doi: 10.1186/ar4386.
INTRODUCTION
Increasing evidence has suggested that linear epitopes of antineutrophil cytoplasmic antibody (ANCA) directed to myeloperoxidase (MPO) might provide clues to the pathogenesis of propylthiouracil (PTU)-induced ANCA-associated vasculitis (AAV). This study mapped epitopes of MPO-ANCA in sera from patients with PTU-induced MPO-ANCA (with or without vasculitis) and primary AAV, aiming to analyze certain epitopes associated with the development of PTU-induced AAV.
METHODS
Six recombinant linear fragments, covering the whole amino acid sequence of a single chain of MPO, were produced from Escherichia coli. Sera from 17 patients with PTU-induced AAV, 17 patients with PTU-induced MPO-ANCA but without clinical evidence of vasculitis, and 64 patients with primary AAV were collected at presentation. Of the 17 patients with PTU-induced AAV, 12 also had sera at remission. The epitope specificities were detected by enzyme-linked immunosorbent assay by using the recombinant fragments as solid-phase ligands.
RESULTS
Compared with patients with PTU-induced MPO-ANCA but without clinical vasculitis, sera from PTU-induced AAV patients showed significantly higher reactivity against the H1 fragment of MPO (optical density values: 0.17 (0.10 to 0.35) versus 0.10 (0.04 to 0.21), P = 0.038) and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P = 0.026). Compared with sera from primary AAV patients, sera from PTU-induced AAV patients had significantly higher reactivity to the P fragment and the H4 fragment (47.1% versus 14.1% P < 0.001; 41.2% versus 14.1%, P = 0.034, respectively), and could recognize a significantly higher number of fragments (two (none to four) versus one (none to two), P = 0.013]. Among the 12 PTU-induced AAV patients with sequential samples, the number of fragments recognized in remission was significantly less than that in initial onset (two (none to four) versus none (none to 0.75), P < 0.001].
CONCLUSIONS
Linear epitopes of MPO molecules might be associated closely with PTU-induced AAV. In particular, the P and H4 fragments may be important epitopes in PTU-induced AAV.
引言
越来越多的证据表明，抗中性粒细胞胞浆抗体（ANCA）针对髓过氧化物酶（MPO）的线性表位可能为丙硫氧嘧啶（PTU）诱导的ANCA相关性血管炎（AAV）的发病机制提供线索。本研究绘制了PTU诱导的MPO-ANCA（伴或不伴血管炎）患者及原发性AAV患者血清中MPO-ANCA的表位图谱，旨在分析与PTU诱导的AAV发生相关的特定表位。
方法
从大肠杆菌中制备了六个重组线性片段，覆盖MPO单链的完整氨基酸序列。收集了17例PTU诱导的AAV患者、17例PTU诱导的MPO-ANCA但无血管炎临床证据的患者以及64例原发性AAV患者就诊时的血清。在17例PTU诱导的AAV患者中，12例在缓解期也有血清样本。以重组片段作为固相配体，通过酶联免疫吸附测定检测表位特异性。
结果
与PTU诱导的MPO-ANCA但无临床血管炎的患者相比，PTU诱导的AAV患者血清对MPO的H1片段反应性显著更高（光密度值：0.17（0.10至0.35）对0.10（0.04至0.21），P = 0.038），且能识别的片段数量显著更多（两个（范围为无至四个）对一个（范围为无至两个），P = 0.026）。与原发性AAV患者的血清相比，PTU诱导的AAV患者血清对P片段和H4片段的反应性显著更高（分别为47.1%对14.1%，P < 0.001；41.2%对14.1%，P = 0.034），且能识别的片段数量显著更多（两个（范围为无至四个）对一个（范围为无至两个），P = 0.013）。在12例有连续样本的PTU诱导的AAV患者中，缓解期识别的片段数量显著少于初始发病期（两个（范围为无至四个）对无（范围为无至0.75），P < 0.001）。
结论
MPO分子的线性表位可能与PTU诱导的AAV密切相关。特别是，P片段和H4片段可能是PTU诱导的AAV中的重要表位。
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