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Am J Transplant ; 14(5): 1173-82, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24730563

RESUMO

Phase III clinical studies have shown that kidney transplant (KT) recipients treated with the costimulation blocker belatacept exhibited a better renal allograft function and lower donor-specific anti-HLA immunization when compared to recipients treated with calcineurin inhibitors (CNI). We analyzed B cell phenotype in KT recipients treated with belatacept and stable renal function (N = 13). Results were compared to those observed in stable patients treated with CNI (N = 12), or with chronic antibody-mediated rejection (N = 5). Both transcriptional profile and phenotypic characterization of peripheral B cells were performed by real-time polymerase chain reaction and flow cytometry, respectively. In belatacept group, the frequency and absolute number of transitional B cells as defined by both phenotypes: CD19(+) CD24(hi) CD38(hi) and CD19(+) IgD(hi) CD38(hi) CD27(-) , as well as naïve B cells were significantly higher compared with CNI group. B cell activating factor (BAFF) and BAFF receptor mRNA levels were significantly lower in belatacept group than in CNI group. These results show for the first time that belatacept influences B cell compartment by favoring the occurrence of transitional B cells with potential regulatory properties, as described in operational tolerant patients. This role may explain the lower alloimmunization rate observed in belatacept-treated patients.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Imunoconjugados/uso terapêutico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Células Precursoras de Linfócitos B/citologia , Transplantados , Abatacepte , Fator Ativador de Células B/genética , Fator Ativador de Células B/metabolismo , Receptor do Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/metabolismo , Células Cultivadas , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Estudos de Coortes , Feminino , Citometria de Fluxo , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Células Precursoras de Linfócitos B/metabolismo , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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