RESUMEN
Pig xenografts represent an alternative source of organs for transplantation. Immunosuppression can prevent rejection, but involves high risk and cost. New anti-rejection techniques have been developed; however, results have not been successful. Few studies have reported xenoantibody levels in xenotransplanted patients with diabetes and no patients have reported a clinical correlation. We analysed anti-galactose (Gal) and other anti-pig antibody (APA) levels in xenotransplanted patients with type 1 diabetes and the relation to the clinical outcome. Twenty-three patients with type 1 diabetes were transplanted with porcine islets inside a device without immunosuppression. Demographic characteristics, insulin dose and xenoantibody levels at different periods were recorded. Anti-Gal and anti-pig antibodies were measured through indirect enzyme-linked immunosorbent assay (ELISA) and haemolytic anti-pig antibody assay. More than 50% were female; the mean current age, current diabetes duration, diabetes duration at xenotransplantation and time post-transplantation were: 20·8, 11, 5·5 and 5·7 years, respectively. Insulin doses remained with a mean reduction greater than 33% in more than 50% of the patients. The lowest anti-Gal antibody levels were related to the highest insulin dose reductions. This relationship could be explained by the device, Sertoli cells and accommodation process.
Asunto(s)
Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Galactosa/metabolismo , Insulina/metabolismo , Trasplante de Islotes Pancreáticos , Adolescente , Animales , Animales Recién Nacidos , Anticuerpos Heterófilos/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Equipos y Suministros , Femenino , Estudios de Seguimiento , Galactosa/inmunología , Supervivencia de Injerto/inmunología , Humanos , Tolerancia Inmunológica , Trasplante de Islotes Pancreáticos/instrumentación , Trasplante de Islotes Pancreáticos/métodos , Masculino , Recuperación de la Función , Células de Sertoli/inmunología , Células de Sertoli/metabolismo , Células de Sertoli/patología , Porcinos , Trasplante Heterólogo , Adulto JovenRESUMEN
Pancreas transplantation is an option to achieve better metabolic control and decrease chronic complications in patients with diabetes. Xenotransplantation becomes an important alternative. In this study, we show the clinical outcome of patients with type 1 diabetes transplanted with neonatal pig islets without immunosuppression. In a longitudinal study of 23 patients with type 1 diabetes, who received porcine islets between 2000 and 2004, we registered demographic and clinical characteristics every 3 months and chronic complications evaluation yearly. Porcine C-peptide was measured in urine samples under basal conditions and after stimulation with l-arginine. More than 50% were female, median current age was 20·8 years, median diabetes duration at transplantation 5·5 years, median current diabetes duration 11 years and median time post-transplantation 5·7 years. Their media of glycosylated haemoglobin reduced significantly after the first transplantation. Insulin doses remain with a reduction greater than 33% in more than 50% of the patients. Before transplantation, 14 of the 21 patients presented mild chronic complications and currently only two patients presented these complications. Porcine C-peptide was present in all urine samples under basal conditions and increased post-stimulation with l-arginine. These patients achieved an excellent metabolic control after the first transplantation. This could explain, as well as the remaining function of transplanted cells, the low frequency of chronic complications compared to patients with similar diabetes duration and age.