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Abstract: TH-PO556

Molecular Imaging of Kidney C3d Deposits to Monitor Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Poppelaars, Felix, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Renner, Brandon, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Foss, Catherine A., Johns Hopkins University, Baltimore, Maryland, United States
  • Laskowski, Jennifer, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Petr, Vojtech, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Kulik, Liudmila, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Pomper, Martin Gilbert, Johns Hopkins University, Baltimore, Maryland, United States
  • Holers, V. Michael, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
  • Thurman, Joshua M., University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States
Background

Early identification of lupus nephritis (LN) is crucial in managing inflammation that could lead to chronic injury and kidney failure, but clinical signs and laboratory tests don't reliably predict histology in LN. Our work focused on using molecular imaging of renal C3d deposition to detect LN at an early stage.

Methods

Biopsy reports were retrospectively analyzed from LN patients to study the link between C3 staining intensity and histology. We also created a monoclonal antibody (mAb 3d29) against human C3d, that cross-reacts with mouse but doesn't bind intact C3. Next, we stained kidney tissue from LN patients and MRL/lpr mice (a model of LN). Lastly, we generated imaging probes from the mAb 3d29 to quantify C3d deposits by optical and positron emission tomography (PET) imaging in live mice.

Results

In LN biopsies, the intensity of C3 deposition correlated with histology. By immunostaining, our mAb 3d29 detected glomerular C3d in kidney samples from MRL/lpr mice and LN patients. In MRL/lpr mice, glomerular C3d deposits were seen at 8 weeks when mice had no histological/functional signs of kidney disease. C3d deposition stepwise increased at 12, 16, and 20 weeks, but showed a decrease at 24 weeks. Next, we performed optical imaging using the 3d29 mAb in Cfh-/- mice, a model of C3 glomerulopathy. Imaging demonstrated high intensities in their kidneys, whereas low signal or only background was detected in wild-type and C3-/- mice. As C3d deposition is an early disease event in MRL/lpr mice, we tested if early C3d imaging could predict future disease severity. Preliminary experiments in MRL/lpr mice suggested that renal C3d deposition detected by imaging at 8 weeks correlated with increased disease activity at 16 weeks. PET imaging in MRL/lpr and control mice with the radiolabeled 3d29 mAb showed similar results.

Conclusion

Renal C3d deposition seems a biomarker of disease activity in LN, and molecular imaging of C3d could be helpful to monitor disease activity in LN patients.

Funding

  • Private Foundation Support