title: Detection of glomerular complement C3 fragments by magnetic resonance imaging in murine lupus nephritis.
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.
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, USA. anna_sargsyan@hotmail.com
authors.forename: Siranush A
authors.initials: SA
authors.lastname: Sargsyan
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Serkova
authors.forename: Brandon
authors.initials: B
authors.lastname: Renner
authors.forename: Kendra M
authors.initials: KM
authors.lastname: Hasebroock
authors.forename: Brian
authors.initials: B
authors.lastname: Larsen
authors.forename: Conrad
authors.initials: C
authors.lastname: Stoldt
authors.forename: Kim
authors.initials: K
authors.lastname: McFann
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Pickering
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Thurman
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism*; D015933:Complement C3d / Q000378:metabolism; D003287:Contrast Media; D018450:Disease Progression; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D019463:Mice, Inbred MRL lpr; D017464:Receptors, Complement 3d
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D058185:Magnetite Nanoparticles; D017464:Receptors, Complement 3d; D003179:Complement C3b; D015933:Complement C3d