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尿单核细胞趋化蛋白-1(MCP-1)是活动性肾血管炎的一个标志物。

Urinary monocyte chemoattractant protein-1 (MCP-1) is a marker of active renal vasculitis.

作者信息

Tam Frederick W K, Sanders Jan-Stephan, George Abraham, Hammad Tarig, Miller Caroline, Dougan Tammy, Cook H Terence, Kallenberg Cees G M, Gaskin Gill, Levy Jeremy B, Pusey Charles D

机构信息

Renal Section, Division of Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.

出版信息

Nephrol Dial Transplant. 2004 Nov;19(11):2761-8. doi: 10.1093/ndt/gfh487. Epub 2004 Sep 7.

Abstract

BACKGROUND

Macrophage infiltration and cytokine production are important in the pathogenesis of crescentic glomerulonephritis in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis. The aim of this study was to investigate whether urinary levels of chemokines, monocyte chemoattractant protein-1 (MCP-1) and fractalkine, were useful tools for non-invasive assessment of renal vasculitis.

METHODS

In a prospective study, concentrations of chemokines were measured in urine and serum samples using specific enzyme-linked immunosorbent assays, and related to the patients' clinical status. Renal expression of MCP-1 was studied by immunohistochemical staining of renal biopsies.

RESULTS

Urinary levels of MCP-1 were significantly higher in patients with active (P<0.01) or persistent (P<0.05) renal vasculitis, in comparison with healthy volunteers, control patients, patients with inactive vasculitis and patients with extra-renal disease only. There were no differences in serum concentrations of MCP-1 between these groups. Reduction in urinary MCP-1 levels following treatment preceded the improvement of renal function by a median of 2 weeks. In one patient, rising urinary levels of MCP-1, despite immunosuppressive therapy, was associated with progression to severe renal failure. There were no differences in urinary fractalkine levels between the different groups of patients and controls. Immunohistology of renal biopsies from patients with crescentic glomerulonephritis showed increased staining for MCP-1 in glomerular and interstitial cells. Urinary MCP-1 levels correlated with glomerular, but not tubulointerstitial, macrophage infiltration (P<0.05).

CONCLUSIONS

This study shows that measurement of urinary MCP-1, but not fractalkine, is a useful non-invasive technique for the assessment of renal involvement and monitoring the response to therapy in ANCA-associated vasculitis.

摘要

背景

巨噬细胞浸润和细胞因子产生在抗中性粒细胞胞浆抗体(ANCA)相关性血管炎所致新月体性肾小球肾炎的发病机制中起重要作用。本研究旨在探讨趋化因子、单核细胞趋化蛋白-1(MCP-1)和fractalkine的尿水平是否为肾血管炎无创评估的有用工具。

方法

在一项前瞻性研究中,使用特异性酶联免疫吸附测定法测量尿液和血清样本中趋化因子的浓度,并将其与患者的临床状况相关联。通过肾活检的免疫组织化学染色研究MCP-1的肾表达。

结果

与健康志愿者、对照患者、非活动性血管炎患者和仅患有肾外疾病的患者相比,活动性(P<0.01)或持续性(P<0.05)肾血管炎患者的尿MCP-1水平显著更高。这些组之间MCP-1的血清浓度没有差异。治疗后尿MCP-1水平的降低比肾功能改善提前了2周。在一名患者中,尽管进行了免疫抑制治疗,但尿MCP-1水平升高与进展为严重肾衰竭相关。不同组患者和对照组之间的尿fractalkine水平没有差异。新月体性肾小球肾炎患者肾活检的免疫组织学显示肾小球和间质细胞中MCP-1染色增加。尿MCP-1水平与肾小球巨噬细胞浸润相关,但与肾小管间质巨噬细胞浸润无关(P<0.05)。

结论

本研究表明,测量尿MCP-1而非fractalkine,是评估ANCA相关性血管炎肾受累情况及监测治疗反应的一种有用的无创技术。

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