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C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.

Sensitized kidney transplant recipients experience high rates of antibody-mediated rejection due to the presence of donor-specific antibodies and immunologic memory. Here we show that transient peri-transplant treatment with the central complement component C3 inhibitor Cp40 significantly prolongs median allograft survival in a sensitized nonhuman primate model. Despite donor-specific antibody levels remaining high, fifty percent of Cp40-treated primates maintain normal kidney function beyond the last day of treatment. Interestingly, presence of antibodies of the IgM class associates with reduced median graft survival (8 vs. 40 days; pā€‰=ā€‰0.02). Cp40 does not alter lymphocyte depletion by rhesus-specific anti-thymocyte globulin, but inhibits lymphocyte activation and proliferation, resulting in reduced antibody-mediated injury and complement deposition. In summary, Cp40 prevents acute antibody-mediated rejection and prolongs graft survival in primates, and inhibits T and B cell activation and proliferation, suggesting an immunomodulatory effect beyond its direct impact on antibody-mediated injury.

Citation: 

Schmitz, Robin, Zachary W. Fitch, Paul M. Schroder, Ashley Y. Choi, Miriam Manook, Janghoon Yoon, Mingqing Song, et al. ā€œC3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.ā€ Nat Commun 12, no. 1 (September 15, 2021): 5456. https://doi.org/10.1038/s41467-021-25745-7.

Published Date: 
Wednesday, September 15, 2021
Published In: 
Nature Communications
PMID: 
34526511