Journal article
Defining Nephritic Factors as Diverse Drivers of Systemic Complement Dysregulation in C3 Glomerulopathy
Kidney international reports, Vol.9(2), pp.464-477
02/2024
DOI: 10.1016/j.ekir.2023.11.025
PMCID: PMC10851021
PMID: 38344720
Abstract
Introduction
C3 glomerulopathy (C3G) is an ultrarare renal disease characterized by deposition of complement component C3 in the glomerular basement membrane (GBM). Rare and novel genetic variation in complement genes and autoantibodies to complement proteins are commonly identified in the C3G population and thought to drive the underlying complement dysregulation that results in renal damage. However, disease heterogeneity and rarity make accurately defining characteristics of the C3G population difficult.
Methods
Here, we present a retrospective analysis of the Molecular Otolaryngology and Renal Research Laboratories C3G cohort. This study integrated complement biomarker testing and in vitro tests of autoantibody function to achieve the following 3 primary goals: (i) define disease profiles of C3G based on disease drivers, complement biomarkers, and age; (ii) determine the relationship between in vitro autoantibody tests and in vivo complement dysregulation; and (iii) evaluate the association between autoantibody function and disease progression.
Results
The largest disease profiles of C3G included patients with autoantibodies to complement proteins (48%) and patients for whom no genetic and/or acquired drivers of disease could be identified (43%). The correlation between the stabilization of convertases by complement autoantibodies as measured by in vitro modified hemolytic assays and systemic biomarkers that reflect in vivo complement dysregulation was remarkably strong. In patients positive for autoantibodies, the degree of stabilization capacity predicted worse renal function.
Conclusion
This study implicates complement autoantibodies as robust drivers of systemic complement dysregulation in approximately 50% of C3G but also highlights the need for continued discovery-based research to identify novel drivers of disease.
Details
- Title: Subtitle
- Defining Nephritic Factors as Diverse Drivers of Systemic Complement Dysregulation in C3 Glomerulopathy
- Creators
- Jill J. Hauer - University of IowaYuzhou Zhang - University of IowaRenee Goodfellow - University of IowaAmanda Taylor - University of IowaNicole C. Meyer - University of IowaSarah Roberts - University of IowaDingwu Shao - University of IowaLauren Fergus - University of IowaNicolo Ghiringhelli Borsa - University of IowaMonica Hall - University of IowaCarla M. Nester - University of IowaRichard J.H. Smith - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Kidney international reports, Vol.9(2), pp.464-477
- DOI
- 10.1016/j.ekir.2023.11.025
- PMID
- 38344720
- PMCID
- PMC10851021
- NLM abbreviation
- Kidney Int Rep
- ISSN
- 2468-0249
- eISSN
- 2468-0249
- Grant note
- DOI: 10.13039/501100011605, name: National Science Foundation; DOI: 10.13039/100000001, name: National Science Foundation, award: 000390183; DOI: 10.13039/100000002, name: NIH; DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: R01 110023
- Language
- English
- Electronic publication date
- 11/2023
- Date published
- 02/2024
- 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; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984539441202771
Metrics
14 Record Views