Elsevier

Kidney International

Volume 81, Issue 2, 2 January 2012, Pages 152-159
Kidney International

Original Article
Detection of glomerular complement C3 fragments by magnetic resonance imaging in murine lupus nephritis

https://doi.org/10.1038/ki.2011.332Get rights and content
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One of the challenges of treating patients with glomerulonephritis is to accurately assess disease activity. As renal biopsies are routinely stained for deposits of C3 activation fragments and glomerular C3 deposits are found in most forms of glomerulonephritis, we sought to determine whether a relatively noninvasive measure of C3 fragment deposition in the kidney can serve as a good biomarker of disease onset and severity. We recently developed a magnetic resonance imaging (MRI)-based method of detecting glomerular C3 and used this to track the progression of renal disease in the MRL/lpr mouse model of lupus nephritis using superparamagnetic iron oxide nanoparticles conjugated to complement receptor type 2 as a targeting agent. Quantitative immunofluorescence showed that glomerular C3b/iC3b/C3d deposition progressively increased with disease activity, a finding replicated by the T2-weighted MRI. The T2 relaxation times decreased with disease activity in the cortex and medulla of the MRL/lpr but not in MRL/Mpj control mice. Thus, MRI contrast agents targeted to glomerular C3 fragments can be used to noninvasively monitor disease activity in glomerulonephritis. As therapeutic complement inhibitors are used in patients with renal disease, this method, should it become feasible in humans, may identify those likely to benefit from complement inhibition.

KEYWORDS

CR2-targeted iron oxide nanoparticles
glomerulonephritis
T2 relaxation time

Cited by (0)

JMT is a consultant for Alexion Pharmaceuticals (Cambridge, MA).

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Current address: National Renewable Energy Laboratory, Golden, Colorado, USA.