Depression of Complement Regulatory Factors in Human and Rat Renal Grafts in Association With Progress of Acute Cellular Rejection
1Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
2Organ Transplantation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Meeting: 2015 American Transplant Congress
Abstract number: A11
Keywords: Graft survival, Kidney transplantation, Rejection
Session Information
Session Name: Poster Session A: Acute Allograft Rejection
Session Type: Poster Session
Date: Saturday, May 2, 2015
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Exhibit Hall E
Introduction and Objective
It is commonly known that complements play important roles in antibody mediated rejection in renal transplantation. However, the association of complements with progression of acute cellular rejection (ACR) has not been fully elucidated. We investigated the expression of complement factors and complement regulatory factors in ACR using rat renal graft models and human renal graft.
Methods
We prepared rat allograft (n=6) and syngenic graft (n=3) models of renal transplantation. The expressions of C1q, C3, C3aR, C4, C5, C5aR, C9, CD55, CD59, and the rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry) over time were assessed in the rat grafts using real-time PCR. We also administered anti-Crry and anti-CD59 antibodies to allograft model rats, and assessed overall survival. Furthermore, we obtained data from 64 human renal transplant recipients treated at our hospital and diagnosed with ACR, and divided them into high and low CD46 expression groups determined by immunohistochemical staining, and assessed the relationship to clinical course.
Results
Real-time PCR results showed that expressions of the complement regulatory factors CD55, CD59, and Crry were gradually diminished in the allograft model, while those were significantly decreased on day 5 after transplantation in comparison with the syngenic model (p <0.01). In contrast, expressions of C1q, C3, C5aR, and C9 were significantly increased in the allograft model over time (p<0.01). The mean survival period for the allograft model was 7.9 days, while that for the anti-Crry antibody model was significantly shortened by 4.4 days (p<0.01) and for the anti-CD59 antibody model was shortened by 5.9 days, which was not significant (p=0.11). In the human ACR cases, the high CD46 expression group had significantly improved serum creatinine at 2 and 12 months after ACR treatment as well as better 5-year graft survival rate, as compared with the low expression group (p<0.05 for each).
Conclusion
Based on our rat model findings, we concluded that when complement regulatory factors are decreased in a renal graft, production of complement factors become uncontrolled, thus aggravating ACR. Human ACR cases with maintained CD46 expression showed good graft prognosis.<<<<
To cite this abstract in AMA style:
Yamanaka K, Kato １T, Kakuta １Y, Abe T, Imamura R, Maeda A, Miyagawa S, Nonomura N. Depression of Complement Regulatory Factors in Human and Rat Renal Grafts in Association With Progress of Acute Cellular Rejection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/depression-of-complement-regulatory-factors-in-human-and-rat-renal-grafts-in-association-with-progress-of-acute-cellular-rejection/. Accessed May 13, 2025.« Back to 2015 American Transplant Congress