Overcoming Hyperacute Rejection of Monkey ABO-Incompatible Renal Transplantation Using a Complement Inhibition-Based Strategy
Institue of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Meeting: 2013 American Transplant Congress
Abstract number: D1517
Background: It has been demonstrated that complement inhibition-based strategy enables renal allograft accommodation and long-term engraftment in donor skin-presensitized monkeys. The effect of the same strategy on monkey ABO-incompatible renal transplantation is unknown.
Methods: KLH-A antigen was synthesized and used to presensitize blood type B monkeys. After anti-A Ab levels had been significantly elevated, renal transplantation was performed using a blood type A monkey as donor. The presensitized recipients were allocated into 2 groups: (1) no treatment (n=3); (2)CsA+MMF+Pred+Yunnan-Cobra venom factor (Y-CVF, 0.05 mg/kg iv. on day -2 and -1, then 0.02 mg/kg iv. every other day from POD 0-13, n=7). ABO-incompatible renal transplantation using non-presensitized recipients (treated with CsA+MMF+Pred) served as controls (n=2). Serum anti-A Ab levels were detected by FACS using cultured A antigen-positive endothelial cells as targets. IgG, IgM, C3c, C4c, C4d, C5b-9, and Fibrin deposition were determined by either Immunohistochemical or immunofluorescence stainning.
Results: ABO-incompatible allografts in non-presensitized control group did not develop hyperacute rejection (HAR) or acute antibody-mediated rejection (AAMR) and survived more than 30 days. Anti-A Ab levels were significantly elevated in most of blood type B monkeys after KLH-A presensitization. Without any treatment, all 3 renal allografts in KLH-A-presensitized control group developed HAR within 1 hours. However, HAR was successfully prevented in all presensitized recipient monkeys by early inhibition of complement with Y-CVF. Three of 7 renal grafts survived more than 30 days without any histologic evidence of humoral rejection. In contrast, 4 other grafts in this group developed AAMR within 1 week in spite of the significant suppression of complement activation, which may be associated with the injury mediated by high levels of induced anti-A Ab through some mechanisms other than classic complement activation passway.
Conclusion: With KLH-A presensitization, HAR was successfully developed in ABO- incompatible renal transplantation in cynomolgus monkeys. The HAR can be prevented using complement inhibition-based strategy. Modified strategy to avoid AAMR and achieve long-term survial in this ABO- incompatible transplant model needs to be further investigated.
To cite this abstract in AMA style:
Chen G, Wang J, Zhong S, Chen S, Wang X, Wang L, Xiang Y, Chen S. Overcoming Hyperacute Rejection of Monkey ABO-Incompatible Renal Transplantation Using a Complement Inhibition-Based Strategy [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/overcoming-hyperacute-rejection-of-monkey-abo-incompatible-renal-transplantation-using-a-complement-inhibition-based-strategy/. Accessed May 17, 2025.« Back to 2013 American Transplant Congress