Asunto(s)
Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Neoplasias de Células Germinales y Embrionarias/patología , Antineoplásicos/uso terapéutico , Niño , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Congenital dyserythropoietic anemias are rare hematological disorders leading to ineffective erythropoiesis with chronic anemia, complicated by iron overload. Here we present a remarkable clinical course of an infant with CDA type II who first presented as a severe fetal hydrops, requiring serial intrauterine red cell transfusions. While postnatal transfusion dependency persisted, the patient was successfully transplanted with a myeloablative conditioning regimen and peripheral blood stem cells of a matched donor. We believe that allogeneic HSCT is a reasonable therapeutic approach for patients with very severe CDA, even if only a matched unrelated donor is available.
Asunto(s)
Anemia Diseritropoyética Congénita/terapia , Transfusión de Sangre Intrauterina , Trasplante de Células Madre , Terapia Combinada , Femenino , Humanos , Lactante , Embarazo , Pronóstico , Acondicionamiento PretrasplanteAsunto(s)
Linfocitos T CD8-positivos , Síndromes de Inmunodeficiencia , Linfocitosis , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Trasplante de Células Madre , Tiazoles/efectos adversos , Aloinjertos , Niño , Infecciones por Virus ADN/sangre , Infecciones por Virus ADN/inducido químicamente , Dasatinib , Humanos , Síndromes de Inmunodeficiencia/sangre , Síndromes de Inmunodeficiencia/inducido químicamente , Recuento de Linfocitos , Linfocitosis/sangre , Linfocitosis/inducido químicamente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Tiazoles/administración & dosificaciónRESUMEN
BACKGROUND: For Thrombasthenia Glanzmann (GT) patients presenting with a severe clinical phenotype due to complete lack of thrombocyte function or increased titres of anti-platelet antibodies hematopoietic stem cell transplantation (SCT) is the only curative therapy. CASE REPORT: We report the case of a 13-month-old boy, presenting with a severe course of GT, who was successfully treated with an HLA-identical sibling bone marrow transplant. SCT was complicated by anti-platelet alloimmunization after platelet transfusion successfully treated with high dosage immunoglobulins (2 g/kg) and partial plasma exchange. CONCLUSION: SCT may be a viable option for selected patients with GT. However, SCT in GT carries its own significant risks, resulting from the development of anti-platelet antibodies. A critical risk-benefit analysis is mandatory prior to SCT.
Asunto(s)
Plaquetas/inmunología , Trasplante de Células Madre Hematopoyéticas , Isoanticuerpos/sangre , Trombastenia/inmunología , Trombastenia/terapia , Aberraciones Cromosómicas , Femenino , Genes Recesivos/genética , Tamización de Portadores Genéticos , Prueba de Histocompatibilidad , Humanos , Inmunización Pasiva , Lactante , Intercambio Plasmático , Pruebas de Función Plaquetaria , Trombastenia/genética , Trasplante HomólogoRESUMEN
Dendritic cell (DC) development and function is critical in the initiation phase of any antigen-specific immune response against tumours. Impaired function of DC is one explanation as to how tumours escape immunosurveillance. In the presence of various soluble tumour-related factors DC precursors lose their ability to differentiate into mature DC and to activate T cells. Gangliosides are glycosphingolipids shed by tumours of neuroectodermal origin such as melanoma and neuroblastoma. In this investigation we address the question of whether gangliosides suppress the development and function of monocyte-derived DC in vitro. In the presence of gangliosides, the monocytic DC precursors showed increased adherence, cell spreading and a reduced number of dendrites. The expression of MHC class II molecules, co-stimulatory molecules and the GM-CSF receptor (CD116) on the ganglioside-treated DC was significantly reduced. Furthermore, the function of ganglioside-treated DC was impaired as observed in endocytosis, chemotactic and T cell proliferation assays. In contrast to monocytic DC precursors, mature DC were unaffected even when higher doses of gangliosides were added to the culture. With regard to their carbohydrate structure, five different gangliosides (GM2, GM3, GD2, GD3, GT1b), which are typically shed by melanoma and neuroblastoma, were tested for their ability to suppress DC development and function. Suppression was induced by GM2, but not by the other gangliosides. These data suggest that certain gangliosides impair DC precursors, implying a possible mechanism for tumour escape.
Asunto(s)
Gangliósidos/farmacología , Monocitos/citología , Tumores Neuroectodérmicos/inmunología , Escape del Tumor , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Quimiotaxis de Leucocito/efectos de los fármacos , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Endocitosis/efectos de los fármacos , Citometría de Flujo , Gangliósido G(M2)/farmacología , Antígenos HLA-D/inmunología , Humanos , Inmunofenotipificación , Prueba de Cultivo Mixto de Linfocitos , Melanoma/inmunología , Monocitos/efectos de los fármacos , Monocitos/inmunología , Neuroblastoma/inmunologíaRESUMEN
Dendritic cells (DC) form a specialized system for presenting Ag to naive or quiescent T cells and consequently play a central role in the induction of T and B cell immunity. In this study we used DC generated from peripheral progenitors to analyze the effect of IL-10 on the accessory function of human DC. We demonstrate that immature DC, harvested on days 9 to 11 and exposed to IL-10 for the last 2 days of culture, show a strongly reduced capacity to stimulate a CD4+ T cell response in an allogeneic MLR in a dose-dependent manner. In contrast, fully mature DC are completely resistant to the effects of IL-10. These results were obtained in both an alloantigen-induced MLR and an anti-CD3 mAb-induced response of primed and naive (CD45RA+) CD4+ T cells. FACS analysis revealed inhibition of the up-regulation of the costimulatory molecules CD58 and CD86 and the specific DC marker CD83 in DC pretreated with IL-10. These data suggest that IL-10 inhibited the development of fully mature DC. Furthermore, DC precultured with IL-10, but not controls, induced a state of alloantigen-specific anergy in CD4+ T cells and of peptide-specific anergy in the influenza hemagglutinin-specific T cell clone HA1.7. Analysis of the supernatants of these anergic T cells revealed a reduced production of IL-2 and IFN-gamma compared with that in control cells. Collectively, these data suggest that IL-10 converts immature DC into tolerogenic APC, which might be a useful tool in the therapy of patients with autoimmune or allergic diseases.