RESUMEN
Leukocyte adhesion deficiency type III (LADIII) is an autosomal recessive disorder that presents with a severe leukocyte adhesion defect and a Glanzmann-type thrombocytopathy. Hematopoietic stem cell transplantation (HSCT)--the only definitive treatment for LADIII--appears to have a high rate of complications. In this study, we describe a new group of patients with LADIII, highlighting further clinical and immunologic aspects of this disease, and reevaluating the effectiveness of HSCT for its treatment. The patients had clinical and laboratory findings consistent with LADIII. Molecular analysis confirmed the presence of a mutation in the kindlin-3 gene. HSCT was carried out in 3 patients and was successful in 2. The diagnosis of LADIII should be considered in all patients who present with recurrent infections and a bleeding diathesis, regardless of the leukocyte count. LADIII is a primary immune deficiency, which can be successfully corrected by bone marrow transplantation if applied early in the course of the disease using appropriate conditioning.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndrome de Deficiencia de Adhesión del Leucocito/terapia , Preescolar , Femenino , Humanos , Lactante , Síndrome de Deficiencia de Adhesión del Leucocito/sangre , Síndrome de Deficiencia de Adhesión del Leucocito/diagnóstico por imagen , Síndrome de Deficiencia de Adhesión del Leucocito/genética , Masculino , Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Neutrófilos/fisiología , RadiografíaRESUMEN
Leukocyte adhesion deficiency II has been described in only 2 patients; herein we report extensive investigation of another patient. The physical stigmata were detected during prenatal ultrasonographic investigation. Sialyl-Lewis X (sLex) was absent from the surface of polymorphonuclear neutrophils, and cell binding to E- and P-selectin was severely impaired, causing an immunodeficiency. The elevation of peripheral neutrophil counts occurred within several days after birth. A severe hypofucosylation of glycoconjugates bearing fucose in different glycosidic links was present in all cell types investigated, demonstrating that leukocyte adhesion deficiency II is not only a disorder of leukocytes but a generalized inherited metabolic disease affecting the metabolism of fucose.
Asunto(s)
Errores Innatos del Metabolismo de los Carbohidratos/metabolismo , Fucosa/metabolismo , Síndrome de Deficiencia de Adhesión del Leucocito/metabolismo , Proteína C-Reactiva/análisis , Cromatografía de Afinidad , Selectina E/metabolismo , Retardo del Crecimiento Fetal/diagnóstico por imagen , Humanos , Lactante , Recuento de Leucocitos , Síndrome de Deficiencia de Adhesión del Leucocito/sangre , Síndrome de Deficiencia de Adhesión del Leucocito/diagnóstico por imagen , Antígeno Lewis X/análisis , Masculino , Neutrófilos/inmunología , Selectina-P/metabolismo , Linaje , Ultrasonografía PrenatalRESUMEN
Radiographic and immunohistochemical analyses were performed in two Holstein heifers with leukocyte adhesion deficiency (BLAD). Severe bone resorption, osteolysis and severe progressive periodontitis in submandibula due to dysfunction of leukocytes in heifers affected with BLAD were demonstrated by radiographic examination. Immunohistochemical analysis of lymph nodes using anti-CD18 monoclonal antibody demonstrated that CD18-positive cells were not found on those from a heifer affected with BLAD, whereas CD18-positive cells were clearly present in lymph nodes from a clinically normal heifer. These characteristic findings support the importance of adherence-dependent leukocyte functions in host defense.
