Epitope analysis of myeloperoxidase (MPO) specific anti-neutrophil cytoplasmic autoantibodies (ANCA) in MPO-ANCA-associated glomerulonephritis.
Epitope analysis of myeloperoxidase (MPO) specific anti-neutrophil cytoplasmic autoantibodies (ANCA) in MPO-ANCA-associated glomerulonephritis.
复制标题
MPO-ANCA 相关性肾小球肾炎中髓过氧化物酶 (MPO) 特异性抗中性粒细胞胞质自身抗体 (ANCA) 的表位分析。
作者：
A. Fujii;K. Tomizawa;Y. Arimura;T. Nagasawa;Y. Ohashi;T. Hiyama;S. Mizuno;K. Suzuki
目的和方法
应用一组重组MPO缺失突变体，通过Western印迹法对20例髓过氧化物酶抗中性粒细胞胞浆抗体（MPO ANCA）相关性肾炎患者血清进行表位分析。19例患者的血清与MPO重链重组体反应，而没有血清与轻链区反应。高频率位点为MPO重链N端附近的Met 341上游区域（Ha区域）、Met 409上游区域（Hb区域）和C端附近的Gly 598下游区域（Hg区域）。表位识别谱分为2组。A组为Ha、Hb、Hg各有1个或2个区域; B组为3个区域均存在。
结果
A组肺泡出血（AH）和肺纤维化（PF）发生率明显高于B组（AH：A组9/13（69.2%），B组1/6（16.7%）p < 0.05，PF：A组13例中10例（76.9%），B组6例中1例（16.7%）p < 0.05，AH和/或PH：A组13例中12例（92.3%），B组6例中1例（16.7%）p < 0.01）。A组缓解期复发率明显高于B组（P < 0.05）。T细胞反应区为Ha、Hb、Hg和MPO重组片段的轻链。观察到较高频率的HLA分型与MHC II类DR 9。
结论
这些结果表明MPO-ANCA识别MPO分子重链的线性位点。表位识别谱与临床特征相关，提示MPO-ANCA相关性肾小球肾炎的发病机制。
AIM AND METHODS
Epitope analysis of sera from 20 patients with myeloperoxidase anti-neutrophil cytoplasmic antibody- (MPO-ANCA) associated glomerulonephritis was examined by Western blotting using a panel set of recombinant deletion mutants of MPO. Sera from 19 patients reacted with recombinants of MPO heavy chain, whereas no serum reacted with the light chain regions. The high frequency sites were regions on the upstream of Met341 (Ha region), on the upstream of Met409 (Hb region) near the N-terminus of the MPO heavy chain and a region on the downstream of Gly598 (Hg region) near the C-terminus. The epitope recognition profiles were classified into 2 groups. Group A, which had 1 or 2 regions in Ha, Hb and Hg, and group B, which had all 3 regions.
RESULTS
Incidence of alveolar hemorrhage (AH) and pulmonary fibrosis (PF) in group A was significantly higher than that in group B (AH: group A 9 of 13 (69.2%), group B 1 of 6 (16.7%) p < 0.05, PF: group A 10 of 13 (76.9%), group B 1 of 6 (16.7%) p < 0.05, AH and/or PH: group A 12 of 13 (92.3%) and group B 1 of 6 (16.7%) p < 0.01). Relapse rate for patients in the inactive stage in group A was significantly higher than that in group B (p < 0.05). T-cell reacted regions were Ha, Hb, Hg and the light chain of MPO recombinant fragments. Higher frequency of HLA typing with MHC class II DR9 was observed.
CONCLUSION
These results indicate that MPO-ANCA recognizes the linear site of the heavy chain of the MPO molecule. The epitope recognition profiles are related to the clinical features, suggesting the pathogenesis of MPO-ANCA-associated glomerulonephritis.