Journal article
Soluble CR1 Therapy Improves Complement Regulation in C3 Glomerulopathy
Journal of the American Society of Nephrology, Vol.24(11), pp.1820-1829
11/2013
DOI: 10.1681/ASN.2013010045
PMCID: PMC3810083
PMID: 23907509
Abstract
Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are widely recognized subtypes of C3 glomerulopathy. These ultra-rare renal diseases are characterized by fluid-phase dysregulation of the alternative complement pathway that leads to deposition of complement proteins in the renal glomerulus. Disease triggers are unknown and because targeted treatments are lacking, progress to end stage renal failure is a common final outcome. We studied soluble CR1, a potent regulator of complement activity, to test whether it restores complement regulation in C3 glomerulopathy.
In vitro
studies using sera from patients with DDD showed that soluble CR1 prevents dysregulation of the alternative pathway C3 convertase, even in the presence of C3 nephritic factors. In mice deficient in complement factor H and transgenic for human CR1, soluble CR1 therapy stopped alternative pathway activation, resulting in normalization of serum C3 levels and clearance of iC3b from glomerular basement membranes. Short-term use of soluble CR1 in a pediatric patient with end stage renal failure demonstrated its safety and ability to normalize activity of the terminal complement pathway. Overall, these data indicate that soluble CR1 re-establishes regulation of the alternative complement pathway and provide support for a limited trial to evaluate soluble CR1 as a treatment for DDD and C3GN.
Details
- Title: Subtitle
- Soluble CR1 Therapy Improves Complement Regulation in C3 Glomerulopathy
- Creators
- Yuzhou Zhang - Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IowaCarla M Nester - Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IowaDanniele G Holanda - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IowaHenry C Marsh - Celldex Therapeutics Inc., Needham, Massachusetts; andRussell A Hammond - Celldex Therapeutics Inc., Needham, Massachusetts; andLawrence J Thomas - Celldex Therapeutics Inc., Needham, Massachusetts; andNicole C Meyer - Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IowaLawrence G Hunsicker - Division of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IowaSanjeev Sethi - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MinnesotaRichard J.H Smith - Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of the American Society of Nephrology, Vol.24(11), pp.1820-1829
- DOI
- 10.1681/ASN.2013010045
- PMID
- 23907509
- PMCID
- PMC3810083
- NLM abbreviation
- J Am Soc Nephrol
- ISSN
- 1046-6673
- eISSN
- 1533-3450
- Publisher
- American Society of Nephrology
- Language
- English
- Date published
- 11/2013
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Nephrology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984007288102771
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