中国血液净化

›› 2010, Vol. 9 ›› Issue (3): 147-151.

• 临床研究 • 上一篇    下一篇

识别不同靶抗原的抗肾小球基底膜抗体与临床表型相关

崔 昭1 贾晓玉1 刘 畅1,2 赵 娟1 杨 瑞1 曲 贞1 郑 欣1 刘章锁2 赵明辉1   

  1. 北京大学第一医院肾内科暨北京大学肾脏病研究所
  • 收稿日期:2009-12-11 修回日期:1900-01-01 出版日期:2010-03-12 发布日期:2010-03-12
  • 通讯作者: 赵明辉

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

CUI Zhao1, JIA Xiao-yu1, LIU Chang1, 2 ZHAO Juan1, YANG Rui1, QU Zhen1, ZHENG Xin1, LIU Zhan-gsuo1, ZHAO Ming-hui1   

  1. 1Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034; 2Department of Nephrology and Rheumatology, The First Affiliated Hospital of Zhengzhou University, Henan 450052, China
  • Received:2009-12-11 Revised:1900-01-01 Online:2010-03-12 Published:2010-03-12

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摘要：

【摘要】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1、2、3、4和5(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3(IV)NC1，56.7%患者同时识别1(IV)NC1，43.3%患者识别2(IV)NC1，53.6%患者识别4(IV)NC1，85.6%患者识别5(IV)NC1。抗3(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，P＜0.05)的独立决定因素。识别5(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% vs 30.0%，P=0.026)，且抗5(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 cytoplasmic antibodies，ANCA)阳性的患者，对1(IV)NC1(7.3% vs 26.2%，P =0.011)和4(IV)NC1(7.7% vs 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3(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5(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。

关键词: 抗肾小球基底膜病, Goodpasture病, 自身抗体, 靶抗原, 临床表型

Abstract:

【Abstract】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 immunofluorescence using normal human renal tissue as the substrates. Sections were pre-treated with 6M urea to unmask the cryptic epitopes, and untreated sections were used to detect natural exposed epitopes. Their associations with clinical and pathological data were analyzed. Results 3 (IV) NC1 could be recognized by sera from all patients, 1 (IV) NCI by 56.7% sera, 2(IV)NC1 by 43.3% sera, 4 (IV) NC1 by 53.6% sera, and 5(IV)NC1 by 85.6% sera. The level of anti-3(IV)NC1 antibodies was the independent risk factor to the level of serum creatinine at presentation (r=0.308, P =0.003) and to the percentage of crescents in glomeruli (r=0.492, P <0.001). Patients with anti-5(IV)NC1 antibodies had a higher recognizing rate to natural exposed epitopes (67.3% vs. 30.0%, P =0.026). The level of anti-5(IV) NC1 antibodies was positively correlated with the percentage of cellular crescents (P =0.013). Patients with positive antineutrophil cytoplasmic antibodies (ANCA) had a lower recognizing rate to 1(IV)NC1 (7.3% vs. 26.2%, P=0.011) and 4 (IV) NC1 (7.7% vs. 24.4%, P=0.023). Conclusion The major target antigen of anti-GBM antibodies is 3(IV)NC, and the level of these antibodies is the independent risk factor to renal damage. Anti-5(IV)NC1 antibodies may recognize natural exposed epitopes on GBM, and these antibodies may play important roles in the pathogenesis of the disease. Anti-GBM antibodies from patients with positive ANCA have a narrow spectrum of target antigens.

Key words: Goodpasture disease, Autoantibody, Target antigen, Clinical phenotype