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

Journal Article (Journal Article)

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; p = 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.

Full Text

Duke Authors

Cited Authors

  • Schmitz, R; Fitch, ZW; Schroder, PM; Choi, AY; Manook, M; Yoon, J; Song, M; Yi, JS; Khandelwal, S; Arepally, GM; Farris, AB; Reis, ES; Lambris, JD; Kwun, J; Knechtle, SJ

Published Date

  • September 15, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 5456 -

PubMed ID

  • 34526511

Pubmed Central ID

  • PMC8443599

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-25745-7


  • eng

Conference Location

  • England