Yang Rui, Hellmark Thomas, Zhao Juan, Cui Zhao, Segelmark Marten, Zhao Ming-Hui, Wang Hai-Yan
Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Beijing 100034, P.R. China.
J Am Soc Nephrol. 2007 Apr;18(4):1338-43. doi: 10.1681/ASN.2006111210. Epub 2007 Feb 28.
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 alpha(IV)NC1 (tNC1); recombinant human alpha1, alpha3, alpha4, and alpha5(IV)NC1 (ralpha1 through ralpha5); 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 ralpha3(IV)NC1. In the double-positive group, 54.0, 66.7, 71.4% of the sera could recognize ralpha1, ralpha4, and ralpha5, respectively, compared with 49.3, 60.6, and 55.6% for patients with anti-GBM antibodies alone. The levels of the antibodies to ralpha3, tNC1, and the alpha3/alpha1 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 E(A), E(B), 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 alpha3(IV)NC1 compared with that of patients with anti-GBM antibodies alone.
肺出血肾炎综合征（GP）的定义为存在抗肾小球基底膜（抗GBM）抗体和快速进行性肾小球肾炎。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在此情况下的病理生理意义，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。使用牛睾丸α(IV)NC1（tNC1）；重组人α1、α3、α4和α5(IV)NC1（ralpha1至ralpha5）；以及三种包含先前定义的表位区域E(A)、E(B)和S2的嵌合蛋白，通过酶联免疫吸附测定（ELISA）检测了205例有或无ANCA的中国GP患者的抗GBM抗体。在205份抗GBM抗体阳性血清中，63份（30.7%）也为ANCA阳性（61份髓过氧化物酶-ANCA和6份蛋白酶3-ANCA，4份为三重阳性）。所有205份血清均识别tNC1和ralpha3(IV)NC1。在双阳性组中，分别有54.0%、66.7%和71.4%的血清可识别ralpha1、ralpha4和ralpha5，而单独抗GBM抗体患者的这一比例分别为49.3%、60.6%和55.6%。双阳性组中针对ralpha3、tNC1的抗体水平以及α3/α1比值均低于单独抗GBM抗体患者（P<0.05）。大多数血清可识别表位区域E(A)、E(B)和S2，但双阳性组对E(A)、E(B)和S2的吸光度值较低（P<0.05）。与单独抗GBM抗体患者相比，双阳性患者的抗GBM抗体谱更广，而针对α3(IV)NC1的抗体水平较低。
