Autoantibodies against Linear Epitopes of Myeloperoxidase in   Anti-Glomerular Basement Membrane Disease

doi:10.2215/CJN.05270515

CORC > 北京大学 > 生命科学学院

	Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti-Glomerular Basement Membrane Disease
	Li, Jian-nan ; Cui, Zhao ; Wang, Jia ; Hu, Shui-yi ; Jia, Xiao-yu ; Guan, Zhe ; Chen, Min ; Xie, Can ; Zhao, Ming-hui
刊名	CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
	2016
关键词	RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS ANTI-GBM ANTIBODIES GOODPASTURE AUTOANTIGEN KIDNEY INJURY RECOMBINATION CYTOPLASM NEPHRITIS ANCA C1Q
DOI	10.2215/CJN.05270515
英文摘要	Background and objectives Approximately 20%-30% of patients with anti-glomerular basement membrane disease present coexisting anti-myeloperoxidase (MPO) autoantibodies. We previously showed the recognition of a linear fragment of the MPO heavy chain N-terminus (H-1, MPO279-409) in plasma from most double-positive patients. Herein, we investigated the frequency of autoantibodies against overlapping H-1-derived linear peptides in plasma from patients with anti-glomerular basement membrane disease. Design, setting, participants, & measurements We synthesized 13 overlapping linear peptides (H-1-1 to H-1-13) covering MPO279-409. We retrospectively collected plasma samples from 67 patients with anti-glomerular basement membrane disease from 1996 to 2012, and we screened them for IgG autoantibodies by ELISA using intact human MPO and the overlapping peptides as antigens, and we further investigated the clinical significance. Autoantibody binding to the linear MPO structure was confirmed by Western blotting. Results We followed up the 67 patients until 2015, with a median follow-up time of 10.0 (2.3-36.0) months, and 56 ESRD events occurred among the 67 patients with follow-up data. Plasma from 23.9% (16) of the patients recognized intact human MPO, whereas 62.7% (42) plasma samples recognized MPO279-409 linear peptides. Of the 13 linear peptides, H-1-4 (44.8%, 30 patients) and H-1-12 (40.3%, 27 patients) exhibited the highest recognition frequencies. Patients with autoantibodies against H-1-11 or H-1-12 (MPO371-400) were older (46.1 +/- 18.8 versus 34.1 +/- 16.6 years; P<0.01), had higher serum creatinine upon diagnosis (median 7.8 mg/dl, interquartile range 4.9-12.6 mg/dl versus median 5.4 mg/dl, interquartile range 2.4-7.3 mg/dl; P=0.02), and had a higher probability of progressing to ESRD; however, multivariate Cox regression analysis showed that H-1-11 or 12 reaction was not an independent risk factor for renal failure (hazard ratio, 1.2; 95% confidence interval, 0.8 to 2.8; P=0.19). Conclusions Autoantibodies against linear peptides of MPO can be detected in the majority of patients with antiglomerular basement membrane disease, and several are associated with disease severity. The potential common pathogenic mechanism between anti-glomerular basement membrane antibodies and anti-MPO autoantibodies in anti-glomerular basement membrane disease requires further investigation.; Chinese 973 Project [2012CB517702]; Natural Science Fund of China [81321064]; National Natural Science Fund of China [81370801, 81370740, 81330020]; Seeding Grant for Medicine and Life Sciences of Peking University [2014-MB-23]; SCI(E); PubMed; ARTICLE; mhzhao@bjmu.edu.cn; 4; 568-575; 11
语种	中文
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/435215]
专题	生命科学学院
推荐引用方式 GB/T 7714	Li, Jian-nan,Cui, Zhao,Wang, Jia,et al. Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti-Glomerular Basement Membrane Disease[J]. CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY,2016.
APA	Li, Jian-nan.,Cui, Zhao.,Wang, Jia.,Hu, Shui-yi.,Jia, Xiao-yu.,...&Zhao, Ming-hui.(2016).Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti-Glomerular Basement Membrane Disease.CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY.
MLA	Li, Jian-nan,et al."Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti-Glomerular Basement Membrane Disease".CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2016).