RESUMEN
Reticular dysgenesis is a rare inherited immunodeficiency characterized by the lack of blood monocytes and neutrophils and low lymphocyte counts, contrasting with normal red blood cell counts and normal or decreased platelet counts. Whether dendritic cells or macrophages, both of which derive primarily from blood monocytes, are affected in this condition remains unknown. We studied 7 patients with reticular dysgenesis. Macrophages were present in normal numbers in the dermis and in the atrophic lymphoid tissues of these patients, proving that at least some subsets of macrophages can differentiate despite very low monocyte counts. By contrast, Langerhans cells, which are CD1a-positive epidermal dendritic cells, were absent in all (n = 5) patients before bone marrow transplantation. After bone marrow transplantation, Langerhans cells were present (n = 2), suggesting that the defect is not related to keratinocyte dysfunction. A split chimeric reconstitution, characterized by the presence of autologous blood monocytes able to differentiate in vitro into CD1a-positive dendritic cells, was observed in a patient who underwent successful engraftment. These results suggest that an intrinsic cell defect is unlikely and that a bone marrow-derived factor may be defective in reticular dysgenesis; it may be responsible for the Langerhans cell defect but not involved in macrophage differentiation.
Asunto(s)
Células de Langerhans/patología , Inmunodeficiencia Combinada Grave/patología , Piel/patología , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Atrofia , Trasplante de Médula Ósea , Diferenciación Celular , Niño , Células Dendríticas/inmunología , Células Dendríticas/patología , Humanos , Inmunohistoquímica , Tejido Linfoide/patología , Macrófagos/inmunología , Macrófagos/patología , Inmunodeficiencia Combinada Grave/inmunología , Inmunodeficiencia Combinada Grave/terapiaRESUMEN
We report two cases of reticular dysgenesis (RD) successfully treated by BMT utilizing T cell-depleted haploidentical marrow grafts. One child failed to engraft after conditioning with ATG, and the other failed two transplant attempts with cyclophosphamide + ATG, and busulfan + cyclophosphamide + ATG, respectively. Donor engraftment was achieved in both patients following treatment with 700 cGy TBI, with or without other agents. These results, taken together with previous reports in the literature, suggest that children with RD may require more intensive conditioning than patients with other types of severe combined immunodeficiency syndrome.