RESUMEN
Allografts used in the repair of congenital heart defects in children induce a persistent broad HLA antibody response. We have previously shown that a 3-month course of mycophenolic mofetil (MMF) significantly reduces the HLA class I antibody response to valved allograft implantation in children. The purpose of this study was to determine if this reduction in HLA antibody persists after discontinuation of MMF. We conducted follow-up (mean 2 +/- 0.5 years) of seven patients who had received allograft placement for repair of congenital heart defects. These patients received 3 months of immunosuppression with MMF following allograft implantation. When compared to historical controls, patients who received MMF following surgery showed a significantly decreased HLA class I antibody response at 2 years postimplantation. This study demonstrates the ability to persistently alter the HLA class I antibody response using 3 months of MMF following allograft implantation in children.
Asunto(s)
Anticuerpos/química , Antígenos HLA/inmunología , Cardiopatías Congénitas/cirugía , Ácido Micofenólico/análogos & derivados , Adolescente , Formación de Anticuerpos , Niño , Preescolar , Citometría de Flujo , Técnica del Anticuerpo Fluorescente Indirecta , Rechazo de Injerto , Antígenos HLA/química , Válvulas Cardíacas/patología , Antígenos de Histocompatibilidad Clase I , Antígenos de Histocompatibilidad Clase II , Prueba de Histocompatibilidad , Humanos , Técnicas Inmunológicas , Inmunosupresores/farmacología , Lactante , Recién Nacido , Ácido Micofenólico/farmacología , Proyectos Piloto , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
BACKGROUND: Valved allografts induce a brisk, broadly reactive human leukocyte antigen (HLA) antibody response in children after implantation. Mycophenolic mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of both T cells and B cells and has been reported to possibly reduce HLA panel reactive antibody (PRA) in sensitized transplant recipients. METHODS: The purpose of this study was to determine whether MMF can blunt the HLA antibody response to valved allografts in children. Eight patients completed (of 28 approached) a pilot study to determine the effects of 3 months of twice daily MMF (600 mg/m(2)/dose) on the HLA antibody response measured before surgery, at 1 month, and at 3 months after implantation. Patients were 7.5 +/- 4 yrs old (mean +/- standard deviation [SD]), with 5 patients undergoing repair of tetralogy of Fallot, 2 Ross procedures, and 1 aortic valve replacement. RESULTS: In contrast to historical controls with a virtual 100% HLA class I PRA response to valved allograft implantation, MMF markedly decreased the HLA class I antibody response at 1 and 3 months postimplantation. In 6 cases where the HLA type of the donor was defined, PRA specificity correlated with incompatible antigens on the allograft. One patient withdrew after 2 weeks due to a sinus infection that was successfully treated with oral antibiotics, and 3 patients had a transient adverse effect of postoperative vomiting. CONCLUSIONS: This study demonstrates the ability to pharmacologically abrogate the HLA class I antibody response to valved allograft implantation in children using MMF.