Renal 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.
Arthritis Res Ther. 2012 Jun 12;14(3):R140. doi: 10.1186/ar3873.
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.
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.
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.
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.
补体系统对于抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）的发展至关重要。特别是 C5a 发挥着核心作用。在这项研究中，我们研究了 AAV 患者的血浆和尿液 C5a 水平以及肾脏 C5a 受体（CD88 和 C5L2）的表达。
纳入 24 例活动期 AAV 患者、19 例缓解期 AAV 患者和 20 例狼疮肾炎（LN）患者。采用酶联免疫吸附试验（ELISA）检测血浆和尿液 C5a 水平，免疫组织化学检测肾脏标本中 CD88 和 C5L2 的染色。
活动期 AAV 患者的血浆 C5a 水平明显高于缓解期患者、LN 患者和正常对照组，活动期 AAV 患者的尿 C5a 水平明显高于缓解期患者和正常对照组，但与 LN 患者无显著差异。AAV 患者肾小管间质的 CD88 染色平均光密度明显低于正常对照组（0.0052±0.0011 对 0.029±0.0042；P=0.005）。AAV 患者肾小球的 C5L2 染色平均光密度明显高于正常对照组（0.013±0.0027 对 0.0032±0.0006；P＜0.001）。AAV 患者的 CD88 染色平均光密度与初始 eGFR 密切相关（r=0.835；P＜0.001）。双标免疫荧光检测提示 CD88 不表达于中性粒细胞、单核细胞或巨噬细胞，但 C5L2 表达于中性粒细胞（或单核细胞）和巨噬细胞。
升高的血浆和尿液 C5a 水平提示人类 AAV 中补体的激活。肾脏 CD88 表达水平可反映 ANCA 相关性肾小球肾炎的疾病严重程度。在 ANCA 相关性肾小球肾炎中，CD88 表达下调，C5L2 表达上调。
