Desensitization and belatacept-based maintenance therapy in pregnancy-sensitized monkeys receiving a kidney transplant.
Sci Adv
; 9(20): eadg1448, 2023 05 19.
Article
en En
| MEDLINE
| ID: mdl-37205758
ABSTRACT
Among sensitized patients awaiting a transplant, females are disproportionately represented, partly because of pregnancy-induced sensitization. Using female NHPs sensitized by pregnancy alone, we examined the efficacy of costimulation blockade and proteasome inhibition for desensitization. Three animals received no desensitization (control), and seven animals received weekly carfilzomib (27 mg/m2) and belatacept (20 mg/kg) before kidney transplantation. All animals received renal allografts from crossmatch-positive/maximally MHC-mismatched donors. Controls and three desensitized animals received tacrolimus-based immunosuppression. Four desensitized animals received additional belatacept with tacrolimus-based immunosuppression. Multiparous females had less circulating donor-specific antibody when compared to skin-sensitized males before transplantation. While females receiving desensitization showed only a marginal survival benefit over control females (MST = 11 days versus 63 days), additional belatacept to posttransplant maintenance significantly prolonged graft survival (MST > 164 days) and suppressed posttransplant DSA and circulating follicular helper T-like cells. This combination of therapies demonstrates great potential to reduce antibody-mediated rejection in sensitized recipients.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trasplante de Riñón
/
Inmunosupresores
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Sci Adv
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos