Abstract: TH-PO0999
Complement Protein Expression Identifies Antibody-Mediated Rejection Subtypes with Chronic Injury and Poor Outcomes, Regardless of Donor-Specific Antibodies
Session Information
- Transplantation: Basic - Immune Biology, Tissue Injury, and Emerging Technologies
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2001 Transplantation: Basic
Authors
- Allen, Maya A., University Health Network, Toronto, Ontario, Canada
- Manion, Kieran, University Health Network, Toronto, Ontario, Canada
- John, Rohan, University Health Network, Toronto, Ontario, Canada
- Konvalinka, Ana, University Health Network, Toronto, Ontario, Canada
Background
Transplantation is the best treatment for end-stage renal disease, but grafts often fail due to antibody mediated rejection (AMR), caused by donor-specific antibodies (DSA) against the graft endothelium. Intriguingly, 50% of patients with kidney microvascular inflammation consistent with AMR do not have DSA.
Methods
To gain insights into the underpinnings of AMR with and without DSA, laser capture microdissection was used to dissect tubulointerstitium and glomeruli of biopsies from 65 DSA+ and DSA- patients, followed by unbiased proteomic analysis on a Q-Exactive HFX mass spectrometer.
Results
GO analysis of differentially expressed proteins between DSA+ and DSA- biopsies showed enrichment of the term “Complement and coagulation cascade” (q<0.01). Unsupervised hierarchical clustering by expression of proteins in this term identified 4 groups in each compartment, regardless of Banff diagnosis. Of clusters in the tubulointerstitium (T1-4), T1 had the highest graft loss, IF/TA, and creatinine at time of biopsy. Poor outcomes were also prevalent in T3, which had the longest time from transplant to biopsy. C3 and C4A expression was increased in T1, whereas expression of C5-C9 and extracellular matrix (ECM) proteins was increased in both T1 and T3. Of clusters in the glomeruli (G1-4), G2 biopsies had the longest time from transplant to biopsy, highest IF/TA scores and occurrence of graft loss. They also had increased expression of IGHM, complement, and ECM proteins. Correlation of ECM and C5 expression was supported by Imaging Mass Cytometry, which showed C5a in the COL4+ basement membranes of chronic AMR.
Conclusion
These results demonstrate the existence of AMR subtypes delineated by complement protein expression. Consistent correlation of C5-C9 with ECM proteins suggests an interaction between complement and ECM remodelling in AMR.