Detection of glomerular complement C3 fragments by magnetic resonance imaging in murine lupus nephritis.
Detection of glomerular complement C3 fragments by magnetic resonance imaging in murine lupus nephritis.
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DOI：
10.1038/ki.2011.332
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发表时间：
2012-01
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
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治疗肾小球肾炎（GN）患者的挑战之一是准确评估疾病活动。我们最近开发了一种基于磁共振成像（MRI）的检测肾小球C3的方法，并假设该试剂可用于监测GN的严重程度。在目前的研究中，我们使用这种成像方法来跟踪狼疮性肾炎（LN）的MRL/lpr小鼠模型中肾脏疾病的进展。靶向剂由与补体受体2型（CR2靶向SPIO）偶联的超顺磁性氧化铁（SPIO）纳米颗粒组成。通过定量免疫荧光或CR2靶向SPIO和T2加权MRI监测逐渐衰老的MRL/lpr和对照小鼠的肾小球C3 b/iC 3 b/C3 d沉积。免疫荧光显示肾小球C3 b/iC 3b随疾病活动度增加而增加。这一发现与T2加权MRI重复：T2弛豫时间减少（SPIO减少T2弛豫时间）与疾病活动在MRL/lpr小鼠的皮质和髓质，但不是对照小鼠。我们的研究结果表明，靶向肾小球C3 b/iC 3b/C3 d的MRI造影剂可用于非侵入性监测GN的疾病活动。此外，治疗性补体抑制剂最近已用于肾病患者，该方法可以鉴定可能受益于补体抑制的患者。
One of the challenges of treating patients with glomerulonephritis (GN) is to accurately assess disease activity. We recently developed a magnetic resonance imaging (MRI)-based method of detecting glomerular C3, and hypothesized that this agent could be used to monitor the severity of GN. In the current study we used this imaging method to track the progression of renal disease in the MRL/lpr mouse model of lupus nephritis (LN). The targeting agent is comprised of superparamagnetic iron oxide (SPIO) nanoparticles conjugated to complement receptor type 2 (CR2-targeted SPIO). Glomerular C3b/iC3b/C3d deposition in progressively aging MRL/lpr and control mice was monitored with quantitative immunofluorescence or with CR2-targeted SPIO and T2-weighted MRI. Immunofluorescence showed that glomerular C3b/iC3b increased with disease activity. This finding was replicated with the T2-weighted MRI: T2-relaxation times decreased (as SPIO reduce T2-relaxation times) with disease activity in the cortex and medullas of MRL/lpr mice, but not of control mice. Our findings demonstrate that an MRI contrast agent targeted to glomerular C3b/iC3b/C3d can be used to non-invasively monitor disease activity in GN. Further, therapeutic complement-inhibitors have recently been used in patients with renal disease, and this method could identify patients likely to benefit from complement inhibition.
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影响因子：
19.6
作者：
Moll, S;Miot, S;Schifferli, JA
通讯作者：
Schifferli, JA
影响因子：
13.6
作者：
Sacks, Steven;Zhou, Wuding
通讯作者：
Zhou, Wuding
影响因子：
5.6
作者：
Gilbert, Hannah E.;Asokan, Rengasamy;Perkins, Stephen J.
通讯作者：
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影响因子：
38.3
作者：
通讯作者：
--
影响因子：
3.5
作者：
Larsen, B. A.;Haag, M. A.;Stoldt, C. R.
通讯作者：
Stoldt, C. R.