Abstract: SA-PO631
Kidney Complement Peptides Are Abundant in Patients With Kidney Disease
Session Information
- Glomerular Diseases: IgA and Complement-Mediated GN
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1301 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Almaani, Salem, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Shapiro, John P., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Madhavan, Sethu M., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Satoskar, Anjali A., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Merchant, Michael, University of Louisville, Louisville, Kentucky, United States
- Klein, Jon B., University of Louisville, Louisville, Kentucky, United States
- Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Parikh, Samir V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Ayoub, Isabelle, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background
Activation of the complement system has been observed in many immune and non-immune kidney diseases. Murine models of renal fibrosis demonstrate that targetting the complement system may be useful in slowing renal fibrosis. In previous work using an agnostic proteomics approach, the complement system was one of the top regulated pathways shared by many kidney diseases. In this study, we aimed to further identify patterns of complement involvement in a variety of kidney diseases.
Methods
Kidney biopsies from 58 patients across several kidney diseases and 25 controls were used. Glomeruli and tubulointerstitium (TI) were isolated using laser-capture microdissection, processed, and submitted for LC-MS/MS. Peptides were analyzed for spectral count quantitation. Spectral counts of complement pathway components were compared between disease and control samples that were analyzed in the same batch using t tests, a raw p-value<0.05 and |log2 fold change|>0.58 were considered significant.
Results
An increase in abundance of common and terminal pathway complement components was noted in the glomeruli and TI across all diseases. An increase in glomerular and TI C2 and C4 abundance was noted in patients with MCD and FSGS, suggestive of classical and/or lectin pathway involvement. A decrease in glomerular complement receptor 1 (CR1), which is typically expressed by podocytes, was universally observed.
Conclusion
Proteomic analysis of a heterogeneous population of kidney diseases identified an increase in complement pathway peptide abundance. An increase in terminal complement pathway components was universally observed and has the potential to be leveraged therapeutically, to slow fibrosis, across a variety of kidney diseases in a manner similar to renin-angiotensin-aldosterone blockade.