Antigen and epitope specificity of anti-glomerular basement membrane antibodies in patients with Goodpasture disease with or without anti-neutrophil cytoplasmic antibodies
Antigen and epitope specificity of anti-glomerular basement membrane antibodies in patients with Goodpasture disease with or without anti-neutrophil cytoplasmic antibodies
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DOI：
10.1681/asn.2006111210
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发表时间：
2007-04-01
影响因子：
13.6
通讯作者：
Wang, Hai-yan
中科院分区：
文献类型：
--
作者：
Yang, Rui;Hellmark, Thomas;Wang, Hai-yan
Goodpasture病（GP）的定义是存在抗肾小球基底膜（anti-GBM）抗体和快速进展的肾小球肾炎。除了抗gbm外，许多GP患者还产生抗中性粒细胞胞浆抗体（ANCA）。为了阐明ANCA在这种情况下的病理生理意义，我们研究了抗gbm抗体的表位和抗原特异性以及ANCA的抗原特异性。牛睾丸a(IV)NC1 (tNC1)；重组人α 1、α 3、α 4和α 5(IV)NC1 (r α 1至r α 5)；采用ELISA法检测205例伴有或不伴有ANCA的GP患者的抗gbm抗体，其中3个嵌合蛋白含有先前确定的表位区域E-A、E-B和S2。205例抗gbm抗体阳性血清中，63例（30.7%）同时呈ANCA阳性（61例髓过氧化物酶-ANCA和6例蛋白酶3-ANCA， 4例为三阳性）。205份血清均可识别tNC1和r α 3(IV)NC1。双阳性组分别有54.0%、66.7%和71.4%的血清能识别r α 1、r α 4和r α 5，而单独抗gbm抗体组的这一比例分别为49.3%、60.6%和55.6%。双阳性组r α 3、tNC1抗体水平及α 3/ α 1比值均低于单独抗gbm抗体组（P < 0.05）。大部分血清能识别E-A、E-B和S2表位区，但双阳性组对EA、EB和S2的吸光度值较低（P < 0.05）。与单独抗gbm抗体的患者相比，双阳性患者抗gbm抗体谱更宽，抗α 3(IV)NC1抗体水平更低。
Goodpasture disease (GP) is defined by the presence of anti-glomerular basement membrane (anti-GBM) antibodies and rapidly progressive glomerulonephritis. Besides anti-GBM, many patients with GP produce anti-neutrophil cytoplasmic antibodies (ANCA). For elucidation of the pathophysiologic significance of ANCA in this setting, epitope and antigen specificity of the anti-GBM antibodies and antigen specificity of ANCA were studied. Bovine testis a(IV)NC1 (tNC1); recombinant human alpha 1, alpha 3, alpha 4, and alpha 5(IV)NC1 (r alpha 1 through r alpha 5); and three chimeric proteins that contain previously defined epitope regions designated E-A, E-B, and S2 were used to examine the anti-GBM antibodies by ELISA in 205 Chinese patients with GP with or without ANCA. In the 205 anti-GBM antibody-positive sera, 63 (30.7%) were also ANCA positive (61 myeloperoxidase-ANCA and six proteinase 3-ANCA, four being triple positive). All 205 sera recognized tNC1 and r alpha 3(IV)NC1. In the double-positive group, 54.0, 66.7, 71.4% of the sera could recognize r alpha 1, r alpha 4, and r alpha 5, respectively, compared with 49.3, 60.6, and 55.6% for patients with anti-GBM antibodies alone. The levels of the antibodies to r alpha 3, tNC1, and the alpha 3/alpha 1 ratio were lower in the double-positive group than that in patients with anti-GBM antibody alone (P < 0.05). Most of the sera could recognize the epitope regions E-A,E-B, and S2, but the absorbance values to EA, EB, and S2 were lower in double-positive group (P < 0.05). Double-positive patients had a broader spectrum of anti-GBM antibodies and lower levels of antibodies against alpha 3(IV)NC1 compared with that of patients with anti-GBM antibodies alone.