Abstract: TH-PO0896
Terminal Complement Proteins Dominate Chronic Active Antibody-Mediated Rejection
Session Information
- Transplantation: Basic Research
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2101 Transplantation: Basic
Authors
- Allen, Maya A., University of Toronto Department of Laboratory Medicine and Pathobiology, Toronto, Ontario, Canada
- Manion, Kieran, University Health Network, Toronto, Ontario, Canada
- John, Rohan, University of Toronto Department of Laboratory Medicine and Pathobiology, Toronto, Ontario, Canada
- Konvalinka, Ana, University of Toronto Department of Laboratory Medicine and Pathobiology, Toronto, Ontario, Canada
Background
Transplantation is the best treatment for end-stage kidney disease, but many grafts fail due to antibody mediated rejection (AMR). Diagnostic criteria includes graft injury, C4d deposition on the endothelium, and circulating donor-specific antibodies (DSA). AMR is stratified into aucte (aAMR) or chronic-active (caAMR), by basement membrane doubling in caAMR. Notably, 50% of patients showing microvascular inflammation consistent with AMR don't have DSA.
Methods
Laser capture microdissection was used to separate tubulointerstitium (TI) and glomeruli of biopsies from 83 DSA+ and DSA- patients with aAMR or caAMR, followed by unbiased proteomic analysis on a Q-Exactive HFX mass spectrometer.
Results
Complement proteins were amongst the most significantly differentially expressed proteins in both compartments (p<0.05). C6, C8B, and C8G were increased in TI of DSA+AMR biopsies compared to DSA-AMR biopsies. Terminal complement proteins were increased in caAMR compared to aAMR. In glomeruli, complement proteins were increased in caAMR. Preliminary imaging mass cytometry shows C5a expression in the basement membranes of 2 biopsies with caAMR, and activated C5b-9 co-stained with IgG.
Conclusion
Increased complement expression and C5a in the basement membranes suggests complement involvement in caAMR.