识别不同靶抗原的抗肾小球基底膜抗体与临床表型相关

目的研究识别不同靶抗原的抗肾小球基底膜(glomerular basement membrane,GBM)抗体与临床表型的关系。方法应用酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA),以重组人a1、a2、a3、a4和a5(IV)NC1为固相抗原,测定97例抗GBM病患者血清中抗体的靶抗原,并分析其与临床病理表现的关系。69例患者血清进一步应用以正常人肾组织为底物的间接免疫荧光法(indirect immunofluorescence,IIF)检测抗体识别的抗原表位的位置。隐匿性抗原表位的暴露采用6M尿素对组织切片进行预处理,天然暴露抗原表位的检测则以未经处理的组织切片作为底物。结果所有患者血清均识别a3(IV)NC1,56.7%患者同时识别a1(IV)NC1,43.3%患者识别a2(IV)NC1,53.6%患者识别a4(IV)NC1,85.6%患者识别a5(IV)NC1。抗a3(IV)NC1抗体的水平是患者确诊时的血肌酐水平(r=0.308,P=0.003)以及肾脏病理肾小球中新月体的比例(r=0.492,P0.05)的独立决定因素。识别a5(IV)NC1的患者血清对天然暴露的抗原表位的识别率较高(67.3%比30.0%,P=0.026),且抗a5(IV)NC1抗体的水平与细胞性新月体的比例呈正相关(P=0.013)。合并抗中性粒细胞胞浆抗体(antineutrophil cy-toplasmic antibodies,ANCA)阳性的患者,对a1(IV)NC1(7.3%比26.2%,P=0.011)和a4(IV)NC1(7.7%比24.4%,P=0.023)的识别率较低。结论抗GBM抗体的主要靶抗原位于a3(IV)NC1,其抗体的水平是肾脏损害程度的决定因素。天然暴露的抗原表位可能与a5(IV)NC1相关,其抗体在疾病的发病机制中可能发挥重要作用。合并ANCA阳性的患者,其抗体识别的靶抗原较少。

Anti-glomerular basement membrane autoantibodies against different target antigens are related to patients' clinical phenotype

Objective To investigate the association between anti-glomerular basement membrane antibodies against different target antigens and the clinical phenotypes of patients with anti-GBM disease.Methods The target antigens of 97 sera from patients with anti-GBM disease diagnosed in our hospitals in the period from 1998 to 2008 were investigated by enzyme-linked immunosorbent assay (ELISA) using recombinant human1,2,3,4 and 5 (IV) NC1 as the solid phase antigens.Sixty-nine sera were further examined by indirect i...