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Updated: May 29, 2026
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Detection of glomerular complement C3 fragments by magnetic resonance imaging in murine lupus nephritis
Siranush A Sargsyan1, Natalie J Serkova, Brandon Renner
1Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, USA. anna_sargsyan@hotmail.com
Insights
Magnetic resonance imaging (MRI) can now detect C3 fragment deposition in the kidneys, offering a noninvasive way to monitor glomerulonephritis disease activity. This breakthrough may help identify patients who would benefit from complement inhibitor therapies.
Area of Science:
- Nephrology
- Medical Imaging
- Immunology
Background:
- Accurate assessment of glomerulonephritis disease activity is crucial for effective patient treatment.
- Glomerular C3 deposits are common in various forms of glomerulonephritis, suggesting their potential as biomarkers.
- Current methods for assessing C3 deposition often involve invasive renal biopsies.
Purpose of the Study:
- To investigate whether a noninvasive magnetic resonance imaging (MRI)-based method can detect glomerular C3 fragment deposition.
- To determine if this MRI method can serve as a biomarker for glomerulonephritis onset and severity.
- To track renal disease progression in a lupus nephritis mouse model using targeted MRI.
Main Methods:
- Development of an MRI-based technique to detect glomerular C3 using superparamagnetic iron oxide nanoparticles conjugated to complement receptor type 2.
- Application of the MRI method in the MRL/lpr mouse model of lupus nephritis.
- Correlation of MRI findings (T2 relaxation times) with quantitative immunofluorescence measurements of C3 deposition and disease activity.
Main Results:
- Glomerular C3b/iC3b/C3d deposition progressively increased with disease activity in MRL/lpr mice.
- T2-weighted MRI accurately replicated the pattern of C3 deposition, showing decreased T2 relaxation times with increased disease activity.
- The observed changes in T2 relaxation times were specific to the MRL/lpr model and not seen in control MRL/Mpj mice.
Conclusions:
- MRI contrast agents targeted to glomerular C3 fragments can noninvasively monitor disease activity in glomerulonephritis.
- This imaging approach shows promise for assessing disease progression and severity.
- The method may help identify patients with renal disease who could benefit from complement inhibitor therapies.
Abstract:
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.
