C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.
Nat Commun
; 12(1): 5456, 2021 09 15.
Article
em En
| MEDLINE
| ID: mdl-34526511
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridonas
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Complemento C3
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Transplante de Rim
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Rejeição de Enxerto
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Sobrevivência de Enxerto
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Macaca mulatta
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Anticorpos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article