High-Activity Classical and Alternative Complement Pathway Genotypes – Association with Donor-Specific Antibody-Triggered Injury and Renal Allograft Survival
1Department of Medicine III, Medical University of Vienna, Vienna, Austria, 2Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary, 3Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria, 4Department of Pathology, Medical University of Vienna, Vienna, Austria, 5Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria, 6Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, 7Alberta Transplant Applied Genomics Centre, University of Alberta, Edmonton, AB, Canada, 8Department of Medicine III, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
Meeting: 2020 American Transplant Congress
Abstract number: 249
Keywords: Biopsy, Genomics, Kidney transplantation, Rejection
Session Information
Session Name: Kidney Chronic Antibody Mediated Rejection
Session Type: Oral Abstract Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:45pm
Presentation Time: 4:27pm-4:39pm
Location: Virtual
*Purpose: Complement may contribute to donor-specific antibody (DSA)-triggered transplant injury. Here, we investigated whether the intrinsic strength of classical (CP) and alternative complement pathways (AP) relates to the pathogenicity of DSA.
*Methods: CP and AP high-activity genotypes were defined according to C4 gene copy number and the presence of functional polymorphisms in C3 (C3102G), factor B (fB32R) and factor H (fH62V) genes. Associations of these genotypes with blood complement profiles and morphologic/molecular rejection features were evaluated in a cohort of 83 DSA-positive patients [antibody-mediated rejection (ABMR): n=47] identified upon cross-sectional screening of 741 kidney allograft recipients ≥180 days post-transplantation. Associations with long-term graft survival were evaluated in a larger kidney transplant cohort (n=660) not enriched for a specific type of rejection.
*Results: In the cohort of DSA-positive subjects, the number of C4 gene copies was related to C4 protein levels in serum and capillary C4d staining, but not ABMR activity. Patients with a high-activity AP complotype, which was associated with complement consumption in serum, showed enhanced microcirculation inflammation [median glomerulitis plus peritubular capillaritis score: 2 (interquartile range: 0-4) vs. 1 (0-2); P=0.037]. In the larger transplant cohort, the same complotype was associated with an increased risk of graft loss [hazard ratio 1.52 (95% confidence interval: 1.02-2.25, P=0.038)].
*Conclusions: Our study suggests a contribution of high-activity complement genotypes to the activity and phenotypic presentation of ABMR. Future studies will have to clarify whether a possible association of AP strength with long-term graft survival relates to enhanced antibody-triggered injury.
To cite this abstract in AMA style:
Reindl-Schwaighofer R, Mezö B, Eskandary F, Heinzel A, Wahrmann M, Doberer K, Heilos A, Bond G, Kläger J, Kozakowski N, Haslacher H, Oberbauer R, Viklický O, Hruba P, Halloran PF, Rusai K, Prohászka Z, Böhmig GA. High-Activity Classical and Alternative Complement Pathway Genotypes – Association with Donor-Specific Antibody-Triggered Injury and Renal Allograft Survival [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/high-activity-classical-and-alternative-complement-pathway-genotypes-association-with-donor-specific-antibody-triggered-injury-and-renal-allograft-survival/. Accessed May 16, 2025.« Back to 2020 American Transplant Congress