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学科主题: 临床医学
题名:
Anti-glomerular basement membrane autoantibodies against different target antigens are associated with disease severity
作者: Zhao, Juan; Cui, Zhao; Yang, Rui; Jia, Xiao-yu; Zhang, Ying; Zhao, Ming-hui
关键词: anti-GBM autoantibodies ; anti-GBM disease ; epitope spreading ; Goodpasture ; renal function
刊名: KIDNEY INTERNATIONAL
发表日期: 2009-11-01
DOI: 10.1038/ki.2009.348
卷: 76, 期:10, 页:1108-1115
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Urology & Nephrology
研究领域[WOS]: Urology & Nephrology
关键词[WOS]: NORMAL RENAL-FUNCTION ; NORMAL HUMAN SERA ; T-CELL EPITOPE ; IV COLLAGEN ; GOODPASTURES-SYNDROME ; AUTOIMMUNE GLOMERULONEPHRITIS ; GBM ANTIBODIES ; ALPHA-3 CHAIN ; IDENTIFICATION ; SPECIFICITY
英文摘要:

Anti-glomerular basement membrane (GBM) autoantibodies are pathogenic in the development of anti-GBM disease. The main target antigen is the non-collagenous 1 domain (NC1) of collagen alpha 3(IV); however, most antibodies can recognize the NC1 of collagens alpha 1, alpha 2, alpha 4 and alpha 5(IV). In this study, we analyzed the target antigens of anti-GBM autoantibodies to determine their relationship to the severity of renal damage. Natural anti-GBM autoantibodies were purified from 10 healthy individuals and from 57 patients with anti-GBM disease who were divided into groups based on the degree of renal damage defined by their serum creatinine at the time of diagnosis. We found that the sera of all 57 patients recognized alpha 3(IV) NC1, while 23, 20, 28, and 48 patients also recognized the NC1 of collagens alpha 1, alpha 2, alpha 4, and alpha 5(IV), respectively. Natural anti-GBM autoantibodies recognized the NC1 of collagens alpha 3 and alpha 4(IV). The sera of 7 patients with the lowest level of renal damage mainly recognized the NC1 of collagens alpha 3 and alpha 5(IV). In the 20 patients with moderate and the 30 with severe renal damage, all five target antigens could be detected and most sera recognized three to five different alpha chains simultaneously. Regression analysis showed that only the level of autoantibodies against the NC1 of collagen alpha 3(IV) was a significant independent risk factor for higher serum creatinine on diagnosis. Our study shows that autoantibodies to the NC1 of collagen alpha 3(IV) were crucial in causing renal damage. Inter-and intra-molecular epitope spreading can occur during the development of human anti-GBM disease. Kidney International (2009) 76, 1108-1115; doi: 10.1038/ki.2009.348; published online 9 September 2009

语种: 英语
所属项目编号: 30700752 ; 30725034
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000271383000013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56513
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: Peking Univ, Div Renal, Dept Med,Hosp 1, Inst Nephrol,Key Lab Renal Dis,Minist Hlth China, Beijing 100034, Peoples R China

Recommended Citation:
Zhao, Juan,Cui, Zhao,Yang, Rui,et al. Anti-glomerular basement membrane autoantibodies against different target antigens are associated with disease severity[J]. KIDNEY INTERNATIONAL,2009,76(10):1108-1115.
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