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Arthritis Res Ther. 2012; 14(3): R140.
Published online Jun 12, 2012. doi:  10.1186/ar3873
PMCID: PMC3446523
C5a and its receptors in human anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
Jun Yuan,1,2 Shen-Ju Gou,1 Jing Huang,1 Jian Hao,1 Min Chen,corresponding author1 and Ming-Hui Zhao1
1Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China
2Renal Division, Department of Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Department of Internal Medicine, Hubei University of Traditional Chinese Medicine, Wuchang 430061, Wuhan City, China
corresponding authorCorresponding author.
Jun Yuan: yjun_92/at/126.com; Shen-Ju Gou: goushenju/at/163.com; Jing Huang: huangjingxmu/at/126.com; Jian Hao: jian_hao8865/at/163.com; Min Chen: leimeng/at/public3.bta.net.cn; Ming-Hui Zhao: mhzhao/at/bjmu.edu.cn
Received November 21, 2011; Accepted June 12, 2012.
Abstract
Introduction
The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a plays a central role. In this study, plasma and urinary levels of C5a as well as renal C5a receptors (CD88 and C5L2) expression were investigated in patients with AAV.
Methods
Twenty-four patients with AAV in the active phase, 19 patients with AAV in the remission phase, and 20 patients with lupus nephritis (LN) were included. Plasma and urinary levels of C5a were measured with enzyme-linked immunosorbent assay (ELISA). The staining of CD88 and C5L2 in renal specimens was detected with immunohistochemistry.
Results
The level of plasma C5a was significantly higher in patients with AAV in the active phase than that in patients in remission, that in patients with LN, and that in normal controls. The urinary C5a level was significantly higher in patients with AAV in the active phase than that in patients in remission and that in normal controls, but not significantly different between patients with active AAV and patients with LN. The mean optical density of CD88 staining in the tubulointerstitium was significantly lower in AAV patients than that in normal controls (0.0052 ± 0.0011 versus 0.029 ± 0.0042; P = 0.005). The mean optical density of C5L2 in glomeruli was significantly higher in AAV patients than that in normal controls (0.013 ± 0.0027 versus 0.0032 ± 0.0006; P < 0.001). The mean optical density of CD88 staining closely correlated with the initial eGFR (r = 0.835; P < 0.001) in AAV patients. Double-labeling immunofluorescence assay suggested that CD88 did not express on neutrophils, monocytes, or macrophages, but C5L2 expressed on neutrophils (or monocytes) and macrophages.
Conclusion
The elevated plasma and urinary C5a levels indicated complement activation in human AAV. The level of renal CD88 expression could reflect the disease severity of ANCA-associated glomerulonephritis. CD88 expression was downregulated, and C5L2 was upregulated in ANCA-associated glomerulonephritis.
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