Langerhans cell deficiency in reticular dysgenesis

Reticular dysgenesis is a rare inherited immunodeficiency characterized by the lack of blood monocytes and neutrophils and low lymphocyte counts, cont rasting with normal red blood cell counts and normal or decreased platelet counts. Whether dendritic cells or macrophages, both of which derive primar ily from blood monocytes, are affected in this condition remains unknown. W e 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 differenti ate despite very low monocyte counts. By contrast, Langerhans cells, which are CD1a-positive epidermal dendritic cells, were absent in all (n = 5) pat ients 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, chara cterized by the presence of autologous blood monocytes able to differentiat e in vitro into CD1a-positive dendritic cells, was observed in a patient wh o underwent successful engraftment. These results suggest that an intrinsic cell defect is unlikely and that a bane marrow-derived factor may be defec tive in reticular dysgenesis; it may be responsible for the Langerhans cell defect but not involved in macrophage differentiation. (Blood. 2000;96:58- 62) (C) 2000 by The American Society of Hematology.