Addition of Anti-CD40 Monoclonal Antibody to Nonmyeloablative Conditioning With Belatacept Abrogated Allograft Tolerance Despite Induction of Mixed Chimerism.
Transplantation
; 103(1): 168-176, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-30113996
ABSTRACT
BACKGROUND:
We recently reported anti-CD40 monoclonal antibody and rapamycin (aCD40/rapa) to be a reliable, nontoxic, immunosuppressive regimen for combined islet and kidney transplantation (CIKTx) in nonhuman primates. In the current study, we attempted to induce allograft tolerance through the mixed chimerism approach using a conditioning regimen with aCD40 and belatacept (Bela).METHODS:
Five CIKTx or kidney transplant alone recipients were treated with aCD40/rapa for 4 months. All recipients then received a conditioning regimen including horse antithymocyte globulin and aCD40/Bela. The results were compared with previous reports of recipients treated with Bela-based regimens.RESULTS:
All 3 CIKTx recipients developed mixed chimerism, which was significantly superior to that observed in the previous Bela-based studies. Nevertheless, all CIKTx recipients in this study lost their islet and renal allografts as a result of cellular and humoral rejection on days 140, 89, and 84. The 2 kidney transplant-alone recipients were treated with the same conditioning regimen and suffered rejection on days 127 and 116, despite the development of excellent chimerism. B lymphocyte reconstitution dominated by memory phenotypes was associated with early development of donor-specific antibodies in 4 of 5 recipients. In vitro assays showed no donor-specific regulatory T cell expansion, which has been consistently observed in tolerant recipients with our mixed chimerism approach.CONCLUSIONS:
Despite displaying excellent immunosuppressive efficacy, costimulatory blockade with anti-CD40 monoclonal antibody (2C10R4) may inhibit the induction of renal or islet allograft tolerance via a mixed chimerism approach.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trasplante de Islotes Pancreáticos
/
Trasplante de Riñón
/
Quimera por Trasplante
/
Antígenos CD40
/
Acondicionamiento Pretrasplante
/
Tolerancia al Trasplante
/
Abatacept
/
Rechazo de Injerto
/
Inmunosupresores
/
Anticuerpos Monoclonales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Transplantation
Año:
2019
Tipo del documento:
Article
País de afiliación:
Marruecos